A NEW CLASS OF drugs for patients with hormone-driven breast cancer has generated additional therapeutic options, including more combination therapies. That’s the basis for excitement around the Food and Drug Administration’s approval of three cyclin-dependent kinase (CDK) 4/6 inhibitors in the last three years, according to Jacqueline Vuky, M.D.

Vuky, an associate professor of medicine at the Oregon Health and Science University School of Medicine, discussed the management of metastatic breast cancer with CDK4/6 inhibitors during an interview at the 2018 

® State of the Science Summit™ on Breast Cancer.

During her talk at the summit, Vuky gave an overview of the three drugs: Ibrance (palbociclib), Kisqali (ribociclib) and Verzenio (abemaciclib). They interfere with the activity of the enzymes CDK4 and CDK6, thus preventing cancer cells from dividing or multiplying. Each drug was approved for use in combination with an aromatase inhibitor (AI) as initial treatment for postmenopausal women whose metastatic cancers are fueled by the hormones estrogen or progesterone, but not by the protein HER2. AIs work by preventing the body’s natural production of estrogen.

In clinical trials, the CDK4/6 inhibitors sparked an improvement in progression-free survival (PFS) — the time until disease grows &mdash; but did not increase length of life. When added to AIs, they led to better outcomes for all eligible patients.

®: Can you share the highlights of your presentation on CDK4/6 inhibitors?

Vuky: CDK4/6 inhibitors are very exciting. We haven’t had a breakthrough with endocrine (hormonal) therapy for metastatic disease or even early-stage disease for a while. For a long time now, we have been trying combinations with endocrine therapy and therapeutic targets. The fact that this is the first combination that has changed median PFS is very exciting for our patients. Giving them more options is why we do clinical research.

How do multiple approvals of CDK4/6 inhibitors affect treatment? 

Much like with other targeted therapies, such as mTOR inhibitors, it is exciting that we have choices, but it does seem that each one is a little different. Although the data show similar efficacy, as well as improvement in median PFS, compared with the standard therapy, each differs in side effects and schedules, and even abilities to bind to CDK4 or 6. We like choices, although we do have to be concerned about the price of all of these drugs and the added side effects compared with AI therapy alone.

If a patient’s disease progresses on a CDK4/6 inhibitor, is there rationale to move them to another?

There are no data yet. We need and would like to have data to inform us and our patients on the effectiveness of this strategy. Since abemaciclib is approved as a single agent and has stronger affinity for CDK6 as opposed to CDK4, there has been discussion that it’s reasonable to consider switching to this drug after progressing on palbociclib or ribociclib (although the study that led to its approval did not include any patients who had progressed on another CDK4/6 inhibitor.)

A very interesting trial is looking at adding a CDK4/6 inhibitor to an AI in patients whose disease is starting to progress. I find that fascinating, and these questions need to be answered.

What are your thoughts on combinations with CDK4/6 inhibitors?

There are some triplet combinations that may overcome resistance to endocrine therapy. We participated in a combination of Kisqali, the mTOR inhibitor Afinitor (everolimus) and the AI Aromasin (exemestane). At least in our patients, it was really well tolerated.

What about the potential of Verzenio plus the immunotherapy Keytruda (pembrolizumab)?

Lilly Oncology has some information on that preclinical data, as well as the neoMONARCH trial, which is the presurgical trial where they looked at Verzenio as a way to prime tumor cells for immune recognition. Results from a phase 1 trial with Verzenio plus Keytruda, an immune checkpoint inhibitor, were presented in December 2017. (The findings suggested the combination sparked responses in some patients with hormone-driven metastatic breast cancer without worsening side effects.)

(For HER2-positive cancers), there are trials combining CDK 4/6 inhibitors plus anti-HER2 therapies such as Herceptin (trastuzumab) and Perjeta (pertuzumab), as well.

Do you have any advice for patients and their physicians who are deciding between agents?

First, I would ask whether the patient needs combination therapy versus AI therapy. We know that there is a subgroup of patients with a good prognosis who might do well with an aromatase inhibitor alone, although the exact way to define such patients remains unclear. Patients who have poor prognostic features, such as a short time from (post-treatment) endocrine therapy to relapse, might do better with combination therapy. That is the first question they have to ask: “Is combination or single-agent therapy better for my case?”

The second thing to do is look at the toxicities; if a patient has an erratic heartbeat or is on a drug to treat this, I would not give Kisqali. I do think there are some clinical judgments to make when looking at different toxicities and tailoring it for patients.

Articles

Drugs in the News

Three CDK4/6 inhibitors have been approved, offering new options to those with metastatic, hormone-driven breast cancer.

Good Things Come in Threes

AMY ROBACH WAKES UP every morning with gratitude. “Thank you for letting me wake up, even if it’s at 4 a.m.,” she joked in an interview with CURE®. That’s when the “Good Morning America” and “20/20” news anchor generally begins her day.

Robach, 45, is a survivor of stage 2 invasive breast cancer. Despite her physician’s disapproval, she made the radical decision to get a double mastectomy. During that procedure, a second malignant tumor was found in her left breast. Today, she remains on tamoxifen, a drug that helps prevent the recurrence of hormone-driven breast cancers.

Like many who come face-to-face with cancer, Robach describes herself as a changed and better person. During the interview, she discussed the physical, mental and emotional challenges that come with diagnosis and survivorship.

®: Can you share what ran through your head after you heard the words “You have breast cancer?”

Robach: When (the radiologist told) me that I had a malignant tumor, that I had breast cancer, everything stopped. It was all in slow motion after that. … I did not handle it gracefully or stoically at all — I completely fell apart. I think there was a gasp. I made crazy noises &mdash; bawling, snorting. I was alone. I knew they found a mass, but I was sure it was benign. So, when she said (those words), it was just so contrary to everything that I was thinking in that moment. It shook me to my core.

What was it like to fight the disease in a very public way?

I found my breast cancer because of “Good Morning America.” My colleague Robin Roberts, who is a breast cancer thriver, persuaded me to have a mammogram in front of about five million people in the middle of Times Square on live television, just to get the word out that women should go and get their mammograms — we believe starting at age 40.

And it turned out to be much more significant for me, because that led to my breast cancer diagnosis. … I knew by sharing my story that I would save lives. I have heard from dozens and dozens of women that my story did just that, and so I encourage every woman to share her story, because it saves people’s lives and it changes the way they live their lives. … I know (sharing your story) is deeply personal, but the love you get back … Yes, it was scary to be public, but I don’t know how I would have gotten through it if I didn’t have the support from thousands of women who were writing, emailing, texting and tweeting me. It felt beautiful.

You continued to work during chemotherapy treatments. What kept you motivated?

I covered the winter Olympics in between rounds three and four. I thought I was going to take some time off at the end, but then I got this big promotion to be the “Good Morning America” news anchor in between rounds five and six — just when I was going to take my foot off the gas because I was feeling it pretty significantly. And then I thought, “Oh my God, I just got my dream job &mdash; I can’t call in sick.” So Robin Roberts helped me choose a way to get chemotherapy on Thursdays. Friday you’re hopped up on all the steroids and drugs they put in you. Saturday and Sunday are rough, rough, rough. And Monday you’re just OK enough to crawl into work. That’s what I did. And just when you’re starting to feel good again &mdash; bam! You get hit again.

The mental impact of chemotherapy is significant. You lose your memory, and you don’t really remember what you’re doing — probably not a good combination for someone on live television. But I wanted to (work) because I kept hearing back from all those women who were watching.

I kind of felt like — whether it was imagined or not &mdash; people were counting on me to show up, so I showed up. … I was on air for two hours, then I went straight home and collapsed. It was important to me to be something other than a cancer patient, and going to work gave me something to wake up for that wasn’t cancer-related.

Cancer can bring not only physical side effects but also psychosocial and emotional effects. Did you experience this?

There are a lot of physical side effects when you have a double mastectomy. You never really regain feeling in your chest, which is a strange thing. In the shower, I used to get the most upset because that’s when I couldn’t pretend. It’s a strange sensation to have the water hit you and you can’t feel it. I remember crying a lot, feeling sorry for myself — like, “These aren’t my body parts.”

For those of us on drug therapy, you get to experience what menopause is like at 40 — 40 is the new 60! … Hot flashes, mood swings, battling weight gain &mdash; it feels very overwhelming. I felt like I turned 40 and lost 20 years. I had to mourn the loss of who I was before and accept who I am now physically.

But mentally — those are the scars that are the hardest to heal and move on from. I was told and warned that when your treatments are over, you’re not going to be celebrating. You might for one day, but then the fear hits you. I’d see grandparents playing with their grandchildren and have dark thoughts: “Will I know mine? Will I play with mine? Will I be that old?” You hear women complain about their wrinkles and you think, “I hope I know what that feels like. How dare she complain about being in her 50s or 60s.”

To control the fear, I think: ‘Live now. All you have is right now. All anyone has is right now.’ … When I feel that fear and pain, and the lump in my throat starts to swell up, I think, “I am well right now. I have everything I need, and I’m going to enjoy the heck out of it.” I’m planning to climb Mount Kilimanjaro for my five-year cancerversary. I think, “What else can I do? What else can I see?”

You have two daughters and three stepsons. What does a cancer diagnosis do to you emotionally, as a mother? Have you or will you discuss cancer prevention/screening with your children?

Once I got diagnosed with cancer, the first and only thought really went straight to my daughters: “How will I tell them?” I reassured them that I wasn’t going anywhere soon — that I had the best doctors in the world. I was gonna fight like hell, and they were going to be right there with me. Things might get rough, and Mom might look a little scary.

They saw me go through this journey with eyes wide open. I tried to hide any despair or fear. I cried a lot of times in the car and shower. I found this strange strength to not fall apart around them.

My two daughters will 100 percent be screened in their 20s. I’m not BRCA1 or BRCA2, but obviously we don’t know all the connections. They will be taking their health seriously. … (However,) it’s important to note that more than 80 percent of patients with breast cancer have zero family history. I thought I couldn’t possibly have breast cancer because it wasn’t in my family. That was a huge wake-up call for me.

What advice do you have patients and survivors?

There is life during cancer treatments, and there is life after cancer treatments. … I know that I could be among the 30 percent of early-stage breast cancer patients who develop metastatic cancer. That is on my mind every day, but I use it for good. I use it to remind myself that time is limited. I live like I’m dying. I know it sounds like a country music song, but it is how I live. That’s how I have inspired my children to live. Everyone around me lives better. We do what we want to do now — we don’t say 10 years from now. I don’t assume I have 10 years, five years or one year. And that makes life so much better.

What’s the first thing you do when you get home from work?

Get into sweatpants! That’s my favorite thing to wear. And I love to cook. I cook every night, especially now that I am ketogenic. I want to make sure that my food is what I want it to be. My little one, who is 12, likes to be my sous-chef. If I make the food, they all have to clean it up. … We try to (have family dinners) every night. It’s tough with teenagers, but it’s an important part of our family ritual.

People Report

After receiving a breast cancer diagnosis, the news anchor reveals the ways in which she is forever changed.

Amy Robach Discusses Her Cancer Experience

WHEN SOMEONE RECEIVES A cancer diagnosis, one of the first questions the patient or a family member asks the oncology team is: How advanced is the disease?

Staging is the process used to summarize how early or advanced a cancer is — whether or not it is curable and, if so, the approximate expected cure rate. Cancers in each area of the body have unique staging systems based on anatomy. In breast cancer, staging involves the size of the tumor and whether it has spread to nearby lymph nodes or other organs (known as metastasis).

Two types of staging are used: clinical and pathological. Clinical staging is done prior to surgery using physical examination and imaging such as mammogram, ultrasound, MRI and/or PET/CT scans. Pathologic stage is assigned after surgery has been performed and the tumor and lymph nodes have been evaluated.

In January 2018, the American Joint Committee on Cancer made significant changes to the breast cancer staging process. Previously, staging was determined strictly from tumor size (T), lymph node involvement (N) and metastasis to other organs (M). Each element was assigned a number from zero to 4, which were combined to give the stage, also described as a number from zero to 4.

As research has proved, tumor biology is an important factor in determining prognosis. To account for this, physicians now look to a patient’s pathology report and include the tumor’s grade and receptor status as factors in staging. The grade, which is determined when the tumor is viewed under a microscope, describes how similar or different the cells look compared with normal breast tissue, measured on a scale from 1 to 3. The receptor status is based on whether the tumor is driven by the hormones estrogen or progesterone or by the growth factor receptor HER2.

Being positive for estrogen and progesterone receptors is a favorable prognostic factor, because it makes patients eligible for five years of treatment with oral endocrine medications that can help decrease the risk of cancer’s recurrence.

HER2-positive tumors are aggressive, but research has brought effective therapy. For example, two targeted agents, Herceptin (trastuzumab) and Perjeta (pertuzumab), interfere with HER2’s activity. These powerful agents work in combination, along with chemotherapy, to shrink the tumor before surgery but are also used after surgery, and they have made the prognosis for patients with this disease subtype much better. Before Perjeta was approved, the introduction of Herceptin alone improved survival rates in this population by one-third. Now that grade and receptor status are considered along with tumor size and lymph node status, breast cancers can be more accurately staged, and this can be beneficial to patients. For instance, before 2018, tumors larger than 3 centimeters always had a stage of 2 or 3. But now, if the tumor has good prognostic features, such as being estrogen- or progesteronepositive, a tumor this size can be assigned a lower stage. For example, the stage has changed for a grade 2, 5.3-centimeter tumor that is nonmetastatic, has spread to one lymph node and is estrogen-, progesterone- and HER2-positive. Previously, this tumor would have been categorized as stage 3a. Now it’s considered stage 1b. A tumor with all the same characteristics except for its smaller size — 3 centimeters &mdash; previously would have been categorized as stage 2b but now is also considered stage 1b.

The improvements in treatments for breast cancer offer patients many advantages.

Evaluating the biologic makeup of a tumor can help oncologists better predict outcomes, assuming standard therapies are used. And seeing a lower stage number can give patients the inspiration and hope they need to stick with their treatments, improving their chances of survival.

Regina Hampton, M.D., FACS, is medical director of the breast center at Doctors Community Hospital in Lanham, Maryland, and a board member of the American Society of Breast Surgeons Foundation. The foundation hosts an informational website for patients, survivors and caregivers (breast360.org).

Speaking Out

Additional factors now help determine a breast cancer’s stage, making prognoses more accurate.

'Setting the Stage' in Breast Cancer

MANY WOMEN WITH HORMONE-DRIVEN early breast cancer can forgo chemotherapy following surgery without worsening their chance of cure, thanks to a test that can pinpoint an individual’s need for the treatment. To help prevent cancer’s recurrence after surgery, women with this disease typically take endocrine treatments that suppress the body’s production or use of the hormone estrogen, and they often also receive chemotherapy. This post-surgical treatment is known as adjuvant therapy.

The tumor tissue test looks for 21 cancer-associated gene mutations and can determine which women have a low risk of recurrence and don’t need chemotherapy and which face a higher risk and can benefit from the treatment.

The findings, presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in June, were generated by the phase 3 TAILORx study. The data are expected to save thousands of women — about 70 percent of those with hormone-driven early breast cancer &mdash; from overtreatment with chemotherapy.

“These are very important data, because this is the most common form of breast cancer in the United States and developed countries, and the most challenging decision we make with these patients is whether or not to recommend adjuvant chemotherapy with all of its side effects and with its potential benefits,” ASCO expert Harold A. Burstein, M.D., Ph.D., of Boston’s Dana-Farber Cancer Institute, said following the presentation. “What the data provided here today show, from this massive National Cancer Institutesponsored trial, is that the vast majority of women who have this test performed on their tumor can be told that they don’t need chemotherapy, and that can be said with tremendous confidence and reassurance.”

The women who participated in the trial had hormone receptor-positive, early-stage breast cancer that did not overexpress the protein HER2. The cancer had not spread to their lymph nodes.

The median age of the participants was 55; 33 percent were 50 or younger. More than half of the patients (57 percent) had intermediate-grade disease, and 63 percent had a 1- to 2-centimeter tumor.

Estrogen receptor (ER)-positive, HER2-negative, nodenegative breast cancer is one of the most common types, accounting for up to 50 percent of cases of the disease, noted lead study author Joseph A. Sparano, M.D., the associate director for clinical research at the Albert Einstein Cancer Center in the Bronx, a bureau of New York City. Up to 30 percent of patients with these tumors typically experience a recurrence within 10 years of initial treatment. Although adjuvant chemotherapy is recommended for these patients, the benefit is typically very small. Across the board in this population without gene profiling, Sparano said, adding chemotherapy to endocrine therapy prevents 3 to 5 percent of the women from developing a breast cancer recurrence within 10 years of initial treatment, as compared with giving endocrine therapy alone.

The 21-tumor gene expression assay, Oncotype DX Breast Recurrence Score test, helps predict the benefit of chemotherapy based on patient scores from zero to 100. Patients with a score of 26 to 100 have a higher risk of recurrence and benefit from adding chemotherapy to endocrine therapy, whereas those with a score of zero to 10 (low risk) derive little, if any, benefit. It’s uncertain whether adding chemotherapy helps patients with scores of 11 to 25 (intermediate risk).

Between April 2006 and October 2010, 10,273 women were registered for the study, which is the largest adjuvant breast cancer trial to date, according to Sparano. “It was performed in six countries, four continents, over 1,100 sites … and includes a total of 30 co-authors,” said Sparano, who also serves as vice chair of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Research Group, which designed and conducted the study.

The participants who could be evaluated were divided into groups based on recurrence score. Those with a low score (1,629 patients) received endocrine therapy alone. Women with a high score (1,389) received endocrine therapy in combination with standard adjuvant chemotherapy.

Of 6,711 women with an intermediate score, 3,399 were randomized to receive just endocrine therapy, and 3,312 were randomized to receive the standard treatment of chemotherapy followed by endocrine therapy. The women were divided into subgroups based on menopausal status, planned chemotherapy, planned radiation and recurrence score groupings of 11 to 15, 16 to 20, and 21 to 25.

Sparano pointed out that the trial followed women in real time and reflected current standards for chemotherapy and endocrine therapy. Burstein added that prior studies employing the 21-gene test were based on older standards, such as age and tumor size and grade. Therefore, the new findings helped validate the role of adjuvant endocrine therapy with or without chemotherapy in the setting of modern regimens.

The study’s primary goal involved assessing rates of invasive-free survival, which refers to the amount of time before cancer spreads into healthy tissues. At nine years, patients with intermediate recurrence scores receiving endocrine therapy alone and chemotherapy followed by endocrine therapy had similar invasive-free survival rates, both close to and far from the disease’s original location. In these women, the invasive-free survival rate was 83.3 percent with endocrine therapy alone and 84.3 percent with endocrine therapy plus chemotherapy.

The two intermediate-score groups also had similar amounts of time without disease recurrence distant from the original site (94.5 percent with just endocrine therapy versus 95 percent with added chemotherapy); time without any recurrence (92.2 percent versus 92.9 percent); and overall survival (93.9 percent versus 93.8 percent).

Among patients with low recurrence scores, there was a 3 percent rate of distant recurrence (for example, spread of the cancer to the lungs, liver or bones) with endocrine therapy alone, and patients in the high-score group had a 13 percent rate of distant recurrence with added chemotherapy. A secondary analysis of the two mid-range recurrence score groups considered factors that may determine which patients would benefit from added chemotherapy. Although there was no significant association between recurrence score and menopause, tumor size or grade (a measurement of the abnormality of cancer cells based on how they look under a microscope), there was an association between recurrence score and age. In women 50 years or younger with a score of 16 to 20, there were 2 percent fewer distant recurrences among those who received chemotherapy compared with those who did not, and 7 percent fewer recurrences in those with a score of 21 to 25 who took chemotherapy versus those who did not.

“The younger women who had a recurrence score of 16 to 25 had some chemo benefit,” Sparano said. “This was information that could drive some younger women who have a recurrence score in this range to accept chemotherapy.”

The TAILORx trial once again confirmed that patients of any age with this type of breast cancer and a score of zero to 10 would be recommended for endocrine therapy alone (16 percent of patients), and all women in this population with a score of 26 to 100 (17 percent) would be recommended for added chemotherapy.

Women over age 50 with a score of 11 to 25 (45 percent) and patients 50 or younger who have a score of 11 to 15 (8 percent) should be given strictly endocrine therapy as an adjuvant treatment.

“In terms of the big picture of the impact on care, application of this test in clinical practice to this population would be estimated to spare chemotherapy in about 70 percent and to select chemotherapy in about 30 percent, on average,” Sparano said. Burstein added that, for the small group of women who are under age 50 and have intermediate scores from 20 to 25, there will be discussion about whether chemotherapy is warranted or whether using an alternative endocrine approach, such as ovarian suppression, might accomplish the same goals.

“The goal of this study was not just to use less treatment; the goal was to tailor treatment … with the idea of saying some women are going to need more of one kind of therapy and less of another, and others will get a different treatment based on the biology of their disease,” Burstein said. “So, this is an extraordinary day for breast cancer doctors and for women who have breast cancer. It allows us to individualize treatment based on extraordinary science, which now has tremendous prospective validation.”

Features

Some women with hormone-driven early breast cancer can skip chemotherapy after surgery.

Avoiding the Chemo Chair

VICKI SINGER WOLF hopes her diet and exercise will help prevent a cancer recurrence. - PHOTO BY KONNOR J. DURANTE

Thirteen years after undergoing a double mastectomy to treat a recurrence of breast cancer, Patti Aluise felt numbness in her lower right jaw. Figuring it was a tooth problem, she went to her dentist, who couldn’t find anything wrong. Then, in March 2014, the numbness came back, and Aluise had shoulder pain, too. Visits to an oral surgeon and a neurologist yielded no answers aside from “probably arthritis.” That October, as the pain grew worse, Aluise made an appointment with a neurologist at Johns Hopkins Medicine in Baltimore, an easy drive from her home.

The neurologist was concerned about Aluise’s cancer history: an initial diagnosis of ductal carcinoma in situ in 1995, followed by lumpectomies in both breasts and radiation, and then the recurrence and mastectomy in 2001. The doctor ordered a full-body CT scan, which revealed that Aluise’s breast cancer had returned and spread to her bones. “Never in my wildest dreams did I think it would be cancer,” says the 66-year-old retired staff assistant for the federal government. With each passing year, Aluise had been confident she was cured, especially because her breasts — where the cancer had originated &mdash; were gone. “I was told I had a 5 percent or lower chance of recurrence. I thought that was good,” she says.

Aluise consulted with an oncologist at Medstar Georgetown University Hospital, who referred her to a trial of a drug in a new class of medicines called CDK4/6 inhibitors, which block breast cancer cells’ ability to divide and proliferate. This drug was combined with an aromatase inhibitor (AI), a medicine commonly used to prevent recurrences of hormone-driven breast cancer. The nodules in her lungs shrank, and the scans she receives about every four months show no signs that the cancer is progressing. She remains on the treatments and had a rod surgically inserted in her right arm to strengthen a bone that was weakened by a metastatic breast cancer lesion and at risk of fracture.

“I’m very pleased,” Aluise says, adding that when it’s time to undergo scans to look for any recurrences, “I still get ‘scanxiety,’ but I’ve been very lucky.”

Even when breast cancer is caught early and successfully treated, all patients face some risk that their disease will return. Particularly in women with estrogen receptor (ER)-positive disease, a recurrence can happen even after two or three decades, and by then, the cancer has metastasized beyond its original site.

The risk of recurrence is based on the original diagnosis and the treatments given to lower the chance that the cancer will come back. In 2017, data were shared from a large analysis of 88 breast cancer trials involving nearly 63,000 women with stage 1 ER-positive breast cancer who received five years of endocrine therapy — tamoxifen for the entire period or for a few years and then followed by an AI &mdash; and no treatment afterward.

The authors concluded that patients with stage 1 disease faced a 13 percent risk of distant recurrence over the next 15 years if their original cancer had not spread to any lymph nodes. That risk grew to 20 percent if one to three nodes were involved and 34 percent if the cancer had spread to between four and nine nodes. Also, the rate of recurrence (the percentage of survivors experiencing recurrences every year) was about the same over time for each risk group, with no signs of tapering off, even over 20 years.

Many studies underway aim to reveal why the disease comes back, but generally, experts believe that breastcancer cells remaining in the body after treatment can circulate in the blood, find a hidden resting place and go dormant for decades. Eventually, something stimulates them to “wake up” and start multiplying; one recent study suggested that inflammation is to blame. By shedding light on this process, the research could lead to better methods for preventing and treating these recurrences.

Some experimental treatments for recurring breast cancer are based on recent research into why dormant breast cancer cells come back to life after several years. One approach focuses on a process called autophagy, in which cells recycle their own components and debris to use as an energy source.

“When breast cancer cells spread and are in a dormant state, we don’t understand the processes they use to survive for days, months, years, decades. The process of autophagy might be important for those cells’ long-term survival,” says Kent Hunter, Ph.D., acting co-chief of the Laboratory of Cancer Biology and Genetics at the National Cancer Institute (NCI). “If that is the case, then the hope is that drugs that interfere with autophagy might be able to be used to eliminate some of those dormant tumor cells, which would reduce the probability that a patient will relapse years later.”

NCI researchers, as well as a separate group at the University of Pennsylvania (Penn), observed autophagy in dormant breast cancer cells taken from mouse models. Then they tested a drug that interferes with autophagy — the antimalarial hydroxychloroquine &mdash; in mice. The results were so promising that Penn researchers, led by Angela DeMichele, M.D., M.S.C.E., a professor of medicine and epidemiology, are testing it in a clinical trial called CLEVER. Some of the participants will take the drug by itself, whereas others will also receive the biological drug Afinitor (everolimus), which is approved in combination with hormonal therapy for advanced hormone receptor-positive breast cancer.

One potential advantage of a preventive treatment that interferes with autophagy is that it may do its job in as little as six months to one year, says Lewis Chodosh, M.D., Ph.D., a professor of cancer biology and medicine at the Perelman School of Medicine at Penn. The SURMOUNT trial there is looking for markers in blood or bone marrow that predict recurrence, which would help identify patients who should get additional treatment. Researchers will measure the prevalence of disseminated cancer cells in the patients’ bone marrow. “If the treatment clears disseminated cancer cells in the bone marrow in six months, they can stop therapy,” Chodosh says. “The question is: Can we measure a decrease in those cells, and then can we measure an improvement in recurrence-free survival?”

Another trial run by Penn researchers, GLACIER, will combine hydroxychloroquine with gedatolisib, an experimental drug that inhibits cell signals involved in tumor growth. It works by blocking two enzymes, PI3K and mTOR, that are involved in signaling.

Another strategy being investigated: treating earlystage breast cancer with immunotherapy to reduce the risk of recurrence. For example, researchers at Memorial Sloan Kettering Cancer Center in New York City are testing a presurgical combination of Yervoy (ipilimumab) plus Opdivo (nivolumab) — immunotherapies known as checkpoint inhibitors that block the activity of certain proteins to help free up the immune system &mdash; with cryoablation, a freezing process that kills cancer cells in patients with early-stage breast cancer. The idea is to train the immune system to recognize the cancer early on and generate long-term “immune memory” to prevent it from coming back.

Breast cancer that recurs several years after the original diagnosis can be difficult to treat with standard therapies, and immunotherapy is also being investigated in that setting. Immunotherapy drugs, particularly checkpoint inhibitors, so far have shown just modest efficacy in metastatic breast cancer. Early evidence suggests that drugs like Keytruda (pembrolizumab), which blocks the checkpoint PD-1, may have be effective in triple-negative (non-hormone-sensitive) breast cancer, and some studies in ER-positive breast cancer are underway. Several other checkpoint inhibitors and therapeutic vaccines are also being tested in metastatic breast cancer.

After treatment for ER-positive breast cancer, it’s standard practice for women to undergo long-term maintenance treatment with pills that suppress estrogen — AIs &mdash; to help prevent recurrence. Typically, these drugs are given for five years, but questions remain about whether longer treatment might bring greater benefit.

“We are not certain if continuing an aromatase inhibitor after taking one for a full five years reduces the risk of recurrence,” says Daniel Hayes, M.D., the Stuart B. Padnos Professor of Breast Cancer Research at the University of Michigan Rogel Cancer Center in Ann Arbor and co-author of the analysis of 88 studies on breast cancer recurrence. “It’s a challenge to advise women as to whether the benefits of additional therapy would outweigh the risks.” These include side effects such as hot flashes, vaginal dryness, and muscle and joint aches and pains, as well as more serious toxicities such as bone loss and fracture, and possibly heart problems.

Both tamoxifen and AIs block estrogen’s ability to drive breast cancer cells but take different approaches. Tamoxifen, which is known as a selective estrogen receptor modulator, interacts with the receptor itself to keep the hormone from activating the cell, whereas AIs reduce estrogen production in postmenopausal women.

Tamoxifen was traditionally prescribed to both premenopausal and postmenopausal women, but now AIs are the standard of care for women with ER-positive, HER2- negative breast cancer — as long as they are naturally post-menopausal or rendered menopausal medically or surgically. The AIs do not work and can in fact be dangerous for women who have functioning ovaries. “We’re seeing improvements across the board with aromatase inhibitors,” says Jennifer Litton, M.D., an associate professor at The University of Texas MD Anderson Cancer Center in Houston. “But now the question is: Should we do 10 years instead of five?”

That decision can be challenging for patients and physicians. Two large studies of tamoxifen published a few years ago suggested that taking the medication for 10 years lowered the incidence of recurrence, reduced breast cancer deaths and improved survival.

However, for women who either take tamoxifen and then switch to an AI or start with an AI right away, the benefits of continuing an AI beyond five years are not so clear-cut. A study published in 2017 tested different strategies in women who had completed five years of either tamoxifen or an AI. The researchers found no difference in how long the women lived, either without disease or overall, whether they took the AI Arimidex (anastrazole) for two years or five years after the initial regimen.

Oncologists are eager to see the results of ongoing studies that are looking at the long-term benefit of prolonged treatment with AIs, Litton says. “Some studies show that seven years might be the sweet spot; others suggest 10 years,” she says. “We need to see further follow-up to understand the differences.”

The idea of using other targeted therapies along with AIs to prevent breast cancer recurrences is catching on, thanks to positive results in patients with advanced disease. In one trial, combining the CDK4/6 inhibitor Ibrance (palbociclib) with the AI Femara (letrozole) reduced the risk of disease progression by 44 percent and improved the time without progression by more than one year, compared with Femara alone. The most common side effects were low white blood cell counts, infections, nausea and fatigue. However, whether CDK 4/6 inhibitors can work in early-stage breast cancer and lower recurrence risk further than hormonal therapy alone remains to be seen, with several large trials in progress.

When Vicki Singer Wolf’s breast cancer returned in 2016 — 21 years after her initial diagnosis and 10 years after one recurrence &mdash; she opted for a double mastectomy, followed by chemotherapy. Now in her second year of treatment with an AI, she is focusing on adopting healthy habits, such as eating a mostly plant- and fish-based diet and exercising regularly. She hopes that these lifestyle changes will both prevent her cancer from coming back and help her deal with the medicine’s side effects, which include occasional joint pain, fatigue and insomnia. “I have three wonderful grandchildren that I’m around a lot. I want to have the energy to play with them,” says Singer Wolf, 60.

Many oncologists who treat breast cancer also are concerned with survivors’ eating habits, encouraging patients to achieve and maintain a healthy weight as a potential way to lower the risk of recurrences. Last year, the Centers for Disease Control and Prevention published a study linking obesity with an increased risk of13 cancers, including of the breast. And several observational studies have suggested that women who eat high-fat foods or gain weight after a diagnosis of breast cancer face an elevated risk of recurrence, particularly if they are postmenopausal.

However, few definitive studies link recurrence risk to body mass index (BMI) or weight loss to achieve a normal BMI, so communicating the benefits of diet and exercise to patients can be challenging, says Lindsay Peterson, M.D., M.S.C.R, an assistant professor and medical oncologist at the Washington University School of Medicine in St. Louis. “Understandably, some patients who are dealing with a breast cancer diagnosis find it difficult to focus on losing weight,” she says. “We’d like to be able to tell them that it will improve their prognosis, but studies to support that statement are currently lacking.”

The data may arrive soon. In one study, 2,400 women who cut their fat intake to 20 percent of daily calories (down from 30 percent) lowered their risk of breast cancer recurrence by 24 percent, compared with women who didn’t change their eating habits. But that was 15 years ago, and evidence in favor of weight loss remains sparse, so Harvard-led researchers are conducting a trial of more than 3,000 women who have been treated for stage 2 to 3 HER2-negative breast cancer and have a BMI of at least 27. The participants will receive either two years of a weightloss intervention program, complete with telephone coaching and exercise goals, or educational materials about weight loss in addition to routine follow-up. The women will be followed for five years, and the researchers hope to find a 4 percent decrease in recurrence risk in those who undergo rigorous weight loss.

Another question that researchers are trying to answer is whether specific genes raise the risk of breast cancer recurrences. Researchers in the Netherlands reported recently that women with BRCA1 gene mutations were 1.5 times more likely to experience recurrences over a 15-year study period than were noncarriers. Women with BRCA2 gene mutations did not face an elevated risk, but people with any BRCA mutation have an overall elevated risk of developing new cancers, including breast tumors that are unrelated to the ones that were initially treated. In 2005, Singer Wolf discovered that she has a BRCA2 mutation, so now she follows a strict surveillance plan for new or recurring cancer. Every three months, she has her blood cell and thyroid levels tested, plus physical exams of her breasts and lymph nodes, as well as regular colonoscopies and skin checkups.

“My body just wants to make cancer — this is a fear I live with,” says Singer Wolf, who helps manage a family e-commerce business and HIS Breast Cancer Awareness, a foundation she launched with her brother to bring awareness to BRCA mutations and cancer risk. “But I still have a lot of life ahead of me.”

After treatment, remaining breast cancer cells can lie dormant for years before causing a recurrence. Researchers are investigating how to stop them.

Lying in Wait: Dealing With Lingering Cancer Cells After Treatment

REBECCA PINE gained a sense of control when she got decorative tattoos on her chest after a bilateral mastectomy. - BEATRICE DE GEA

Rebecca Pine feels empowered every time she catches sight of her bare chest in the mirror. A tattoo of a dragonfly masks a mastectomy scar on her right side, and a lotus tattoo sits just below a similar scar on the left. “These images resonated with me because both the dragonfly and the lotus flower are about transformation,” says the Merrick, New York, resident, who received a diagnosis of stage 1 invasive ductal carcinoma breast cancer in 2009 at age 33. “The dragonfly starts life underwater. It crawls onto land when it matures, unfolds its shimmering wings and takes flight. The lotus needs muddy waters to form its beautiful blossoms.”

Pine spent several years thinking about the artwork she wanted to have permanently sketched on her chest before seeking the services of a tattoo artist in 2015. She’s among a growing number of women affected by breast cancer who are choosing to transform their post-surgery bodies into works of art.

Mastectomy tattoos, sometimes called paramedical body art, serve many purposes: They conceal scars, make a symbolic statement, restore a sense of normalcy to reconstructed breasts that may lack shape or nipples, and provide a sense of control to women who’ve had cancer or who’ve had surgery because they’re predisposed to the disease. “I didn’t have a say about having cancer or losing my breasts,” Pine says, “but I could choose how I wanted to look and feel about myself going forward.”

Tattooing of nipples and areolae following breast reconstruction surgery has been done for years. Over time, tattoo artists, plastic surgeons and other professionals have honed their skills to create tattooed nipples that appear three-dimensional. “A skilled tattoo artist can create the illusion of depth and protrusion using different shades of ink,” says Holly Feneht, a tattoo artist and owner of The Gilded Lily (gildedlilydesign.com), a paramedical body art studio in Santa Clarita, California.

When a nipple-sparing mastectomy isn’t feasible, women undergoing breast reconstruction who want the appearance of nipples can either get a nipple tattoo or undergo another surgery to rebuild the nipple and areola using tissue taken from the newly created breast or another part of the body, such as the thigh. Even with this surgery, a nipple tattoo is often necessary to make the reconstructed breast look more natural.

Most of the women who come to Feneht for postreconstruction nipple tattoos are referred by their plastic surgeons or oncologists. They range in age from 20 to 80, and many are getting tattoos for the first time. “They want a nipple tattoo so they will look more like their natural selves,” Feneht says. In addition, a growing number of women are foregoing the nipple tattoo in favor of a decorative image.

MICHELLE LINDLE got a floral tattoo on one reconstructed breast because her nipple could not be preserved. She learned she had breast cancer after a horse-riding accident left her with a bruised chest, which attracted her attention to a growing lump there. - PHOTO COURTESY OF MICHELLE LINDLE

Michelle Lindle, of Newbury Park, California, sought Feneht’s services after undergoing a double mastectomy and reconstructive surgery in 2015 to treat stage 2 HER2-positive breast cancer. Lindle was able to keep her right nipple and chose to adorn her nipple-less left breast with a colorful array of delicate flowers. “After the trauma of surgeries and chemotherapy, a tattoo can help you feel prettier and more feminine,” Lindle says. “It also gives you a sense of regaining control of your body and what is happening to it.”

Whether clients want nipple or decorative tattoos, Feneht encourages taking small steps. “We can always make a decorative tattoo larger and more extravagant or add more color saturation to a nipple or areola,” she says.

The time and cost involved depend largely on the tattoo’s size and details, as well as the person doing the work. On average, tattoo artists charge from $120 to $200 per hour. Nipple and areola tattoos can take up to two hours, with a second session used as a follow-up to make minor alterations to color saturation and size. Depending on the size of a decorative tattoo, multiple sessions lasting two hours or longer may be needed.

The very act of puncturing skin with a needle to inject ink puts a person at risk of infection; however, no evidence suggests that getting a tattoo poses a major health problem, increases the risk of cancer or recurrence, or interferes with breast cancer screenings. “Women who have had radiation treatments or who have extensive scarring have a slightly higher risk of infection because the skin is more fragile,” says Emily Clark, a physician assistant at Memorial Sloan Kettering Cancer Center in New York City.

Rarely, a person may have an allergic reaction to the tattoo ink, which is made from a mixture of organic pigments and natural preservatives. Signs of infection or other problems include fever; yellow or green discharge; muscle aches; and prolonged, severe redness, pain and swelling at the tattoo site. (Some degree of redness and swelling for just a day or two is normal.)

Clark recommends waiting three to five months after breast surgery before getting a tattoo and always consulting a doctor first. “The surgical incisions should be fully healed. Scars that are still healing won’t absorb tattoo pigment well and may be more prone to infection,” she says. Even patients with lymphedema — fluid retention in limbs due to the removal of lymph nodes &mdash; can get chest tattoos, just not on affected arms or legs. “Tattooing doesn’t increase the risk of complications from lymphedema,” Clark says. “But again, you should always consult with your physician to make sure that tattooing doesn’t pose a problem.”

After radiation, it’s important to delay tattoos until any radiation dermatitis (redness or skin breakdown) has cleared up and avoid tattooing any folds in the skin, which tend to be more affected by radiation therapy. A doctor may prescribe antibiotics to decrease infection risk and, if requested, a topical numbing cream to use an hour before the procedure. “Tattooing is generally less painful for women who have had mastectomies, because the nerves in breast skin are somewhat numb,” Clark says. Expect to feel some pressure and vibrations, as well as a bit more pain or discomfort in nonsurgical areas.

For those heading to a medical office for a tattoo, Feneht recommends finding out what type of ink will be used. “Many medical professionals use cosmetic inks and pigments. Cosmetic ink is ground finer and has smaller molecules than permanent ink, which means your body will break down the ink faster,” she says. As a result, a nipple tattoo could fade away within two years. Tattoos made with permanent ink may need an occasional touchup but should last forever.

It’s up to health insurers to decide whether to cover nipple and areola tattooing performed at a medical facility, plastic surgeon’s office or tattoo studio, and patients may need to fight for it. “In most cases, if a nipple tattoo is performed by a medical professional, it will be covered by the patient’s insurance,” Clark says. “However, patients should speak with their insurance carriers regarding coverage for this procedure.”

SUSAN SAYLES got a temporary henna tattoo after losing her hair due to chemotherapy. - PHOTO COURTESY OF SUSAN SAYLES

The availability of coverage for body art created in tattoo studios, as opposed to in medical settings, varies. Some insurers consider nipple and areola tattoos labeled “paramedical” eligible for coverage, but companies typically don’t pay for decorative tattoos, Feneht says.

Some women simply aren’t comfortable with the idea of having a drawing or saying permanently displayed on their skin. For them, temporary henna tattoos are an option.

Henna is a natural dye that comes from a flowering shrub that grows from North Africa to the Middle East to South Asia. In India, the art of staining the skin with henna is known as mehndi. “Henna has been used for body art for about 5,000 years. It’s a tradition that’s said to bring joy and blessings to the wearer,” says Danila Marilú, a henna artist in Dallas who creates henna crowns on women who have lost their hair to cancer treatments.

About three weeks after her first chemotherapy session, Dallas resident Susan Sayles shaved what was left of her hair and went to Marilú for a henna crown. “People can’t tell from looking at you if you have diabetes or heart disease, but there’s no way to hide a bald head on a woman and all that it represents. I knew people would stare. I figured I might as well give them something to look at,” says Sayles, who was 58 and working as a nurse manager at Texas Oncology when she received a diagnosis of stage 2b breast cancer. “I felt proud while sporting my henna crown. I took a negative situation and did something courageous.”

During the process, a henna artist draws intricate designs on a woman’s scalp using henna paste. The wearer keeps the design moist for six to 12 hours with a mixture of sugar and lemon juice or water, and then uses a towel to slough off the hardened paste. A reddish-brown stain remains. Henna tattoos can last three weeks or longer, depending on upkeep and activities — sweat and water cause faster fading. Wearing a shower cap and regularly applying coconut oil helps the stain last longer. Henna also can be used on eyebrows, although the effects last only about two weeks.

Not all products labeled as henna are safe, however. “Henna that’s black often contains a hair dye called paraphenylenediamine, or PPD, that can cause dangerous skin reactions in some people,” says henna artist Amanda Joy Gilbert, owner of Henna Crowns of Courage (crownsofcourage.org), a nonprofit organization in Grand Rapids, Michigan. Henna should always be dark brown when applied. It will dry to a bright orange stain that oxidizes to a reddish-brown tint in 48 to 72 hours. “Your skin is your largest organ, so you definitely want to use the safest henna,” Gilbert says. Professional henna artists make their own paste, mixing the dye with other natural ingredients, such as lavender essential oil, lemon juice, sugar and water. One way to ensure getting the safest stain is to ask the artist for a list of ingredients and share it with a doctor prior to getting the tattoo.

Depending on the design, getting a henna crown can take anywhere from 90 minutes to three hours. “Your scalp is very sensitive, so initially it feels a bit cold and ticklish,” Sayles says, “but then it becomes a soothing, almost therapeutic experience.” Fees vary but typically start around $100 per hour. Some organizations, such as Henna Crowns of Courage, provide free henna crowns to women and children undergoing cancer treatments. Others that provide this service for free are SARAHENNA in Washington state (www.sarahenna. com/crowns) and Henna Me Beautiful in the Santa Barbara and Northridge areas of California (hennamebeautiful. com/henna-crowns.html).

Before doing a crown, Gilbert spends time with a client and her loved ones to get a sense of who she is as a person. “I might incorporate certain words or phrases into the design, sort of like an empowering mantra,” she says. Gilbert notes that, in the Hindu tradition, henna designs symbolize awakening the inner light. “It’s a joy for me to bring out the inner light of women who have been through so much by giving them a crown of courage,” she says.

After surgery for breast cancer or its prevention, tattoos can bring beauty, confidence and renewal.

The Art of Transformation After a Cancer Diagnosis

SYLVIA MORITZ has taken up a varied exercise routine that helps ease her arthralgia. - PHOTO BY MARIA DEFORREST

For some survivors of certain breast cancers, a treatment to prevent recurrence leads to joint pain so severe that they choose to stop taking the drug. But researchers now advise better ways to cope: getting more exercise or trying acupuncture.

The drugs in question are known as aromatase inhibitors (AIs) and are often used after primary treatment, such as surgery, to help prevent recurrence in postmenopausal survivors who have estrogen receptor (ER)-positive breast cancers. By suppressing estrogen, these once-a-day pills help keep recurrences and new cancers at bay and help prevent death from the disease, but for about half of the women who take them, they do so at a painful price — a side effect known as arthralgia, a catch-all term for joint pain and stiffness.

It’s a price that not all survivors are willing to pay, which is why those researching exercise and acupuncture to relieve this side effect are hopeful that the strategies will encourage more women to stick with their AI regimens.

Arthralgia is one of the most common reasons women discontinue taking these drugs, says Dawn Hershman, M.D., M.S., leader of the breast cancer program at the Herbert Irving Comprehensive Cancer Center at New York- Presbyterian Columbia University Medical Center in New York City. Just 50 percent of women prescribed an AI take it at least 80 percent of the time for the recommended full five years, she says, and 25 percent discontinue the drugs. Because arthralgia is not permanent, it typically disappears when treatment stops.

“These women are taking medication to prevent something that might not happen,” Hershman says. “If you’re feeling pain, it’s hard to be motivated to do that.”

Yet there are convincing reasons to persevere. A 2011 study examined adherence to AIs or tamoxifen — another kind of hormonal treatment &mdash; and health outcomes in more than 8,700 women with hormone-sensitive breast cancer. The results revealed that, at 10 years, estimated survival was 80.7 percent for women who continued hormonal therapy compared with 73.6 percent for those who stopped. Among those who continued the drugs, survival at 10 years was 81.7 percent in those who adhered to their regimens versus 77.8 percent in women who did not.

“Both early discontinuation and nonadherence to hormonal therapy were common and associated with increased mortality,” wrote Hershman, the lead author, and her colleagues. “Interventions to improve continuation of and adherence to hormonal therapy may be critical to improve breast cancer survival.”

Researchers aren’t sure what’s behind the joint pain and stiffness that occur in many women who take AIs. Amy Comander, M.D., a medical oncologist at the Massachusetts General Hospital Cancer Center-affiliated Vernon Cancer Center in Newton, Massachusetts, and medical director of the Auerbach Breast Center at Newton- Wellesley Hospital, says that although it can be difficult to sort out the origin of joint pain, estrogen plays an important role in the body and overall bone health. AIs — Femara (letrozole), Arimidex (anastrozole) and Aromasin (exemestane) &mdash; work to lower estrogen levels. When the hormone is suppressed, arthralgia symptoms can develop quickly.

It’s not easy for doctors to predict who might develop AI-induced arthralgia. Researchers have not pinpointed any clear signals that the condition will develop, although study results do suggest a few signals: previous treatment with hormone replacement or chemotherapy, being menopausal for five years or less and having pre-existing joint problems. Taking tamoxifen before an AI, on the other hand, has been found to potentially reduce a woman’s likelihood of experiencing arthralgia.

Sylvia Moritz, 62, of Ocean View, Delaware, says her arthralgia began “almost immediately” when she started taking Femara, which her oncologist prescribed after she was treated for invasive micropapillary carcinoma, an ER-positive breast cancer. “I could feel it building up over the first three to four weeks,” she says.

Fortunately, promising evidence supports two medication- free methods for managing arthralgia discomfort: exercise and acupuncture. Exercise’s beneficial effects on weight control, mood and general well-being are often cited, and the yearlong HOPE (Hormones and Physical Exercise) study, published in 2015 in the Journal of Clinical Oncology, examined whether it could also help relieve the severity of AI-induced arthralgia in 121 survivors of breast cancer.

“We found exercise to be associated with a 30 percent improvement in arthralgia associated with AI use,” says lead author Melinda Irwin, Ph.D., M.P.H., a professor of epidemiology at the Yale School of Public Health and an associate director of the Yale Cancer Center in New Haven, Connecticut. At the study’s outset, women rated their arthralgia pain on a scale of zero to 10, all reporting a 3 or higher. Those who spent a year in the study’s exercise group experienced an average decrease in pain of 1.6 points, whereas those in the group receiving usual care (no prescribed exercise) experienced a 0.2-point increase in pain. “Many of the women who participated in our study were concerned about exercising, as they thought this would increase their joint pain, but after just a couple months of following our exercise program, they were physically stronger, activities of daily living were easier, and they had less pain,” Irwin says.

Moritz attests to the positive impact of exercise in managing her arthralgia symptoms. Her oncologist told her to expect some joint pain, particularly in her hips, knees and fingers, when she began taking Femara. But the pain was excruciating, she says, especially if she sat for a long time. Her doctor encouraged her to exercise.

SYLVIA MORITZ finds that knitting helps control arthralgia in her hands. - PHOTO BY MARIA DEFORREST

“Standing up could be an exercise in torture,” Moritz says. But the worst pain was in her fingers. Following the advice of a friend, she took up knitting as a way to exercise her hands. “It was the only thing that would keep my fingers moving and relieve the pain,” she says.

She also began walking and added weight training. “That helped because I started to build muscle mass, which took the strain off my joints,” she says. “My joints still hurt, but they hurt a lot less. The pain didn’t go away, but exercise alleviated it to the point where I was functional.”

Today, Moritz, who finished a five-year course of AIs, still walks 5 miles every day, lifts weights a few times a week and pedals her bicycle through her neighborhood. She encourages others dealing with arthralgia to just keep moving. Moritz’s exercise regimen is in line with the program used in the HOPE study. Participants walked briskly outside or on a treadmill and performed six common strength-training exercises: leg presses, leg extensions, leg curls, bench presses, pull downs and seated rows. The exercises can be done at a gym, but Irwin also recommends finding out if a local YMCAs offer the Livestrong Program, a free or low-cost exercise plan that gives cancer survivors the opportunity to work with certified personal trainers (livestrong.com). “This will allow them to learn how to exercise safely and at the appropriate intensity, in turn improving their arthralgia and other cancer outcomes,” Irwin says.

Comander says she typically asks patients to describe their pain and might prescribe an exercise program similar to the one used in the study. “Many say, ‘I get out of bed in the morning and I feel like an old lady,’” she says. “Some people feel pain not just in the morning but all day. I try to get a sense of how severe the pain is.”

Hospital programs can help people who haven’t exercised regularly learn how to do it safely and effectively, Comander says. Her facility offers a staff physiatrist — a physician specializing in physical medicine and rehabilitation &mdash; who helps uncover sources of joint pain and creates strategies to manage it, including exercise such as yoga, Pilates, walking, Zumba, tennis, swimming or biking. Physical therapy might also be recommended.

JODI MONROE bikes and competes in dragon boat races to help control her arthralgia. - PHOTO BY ANNABEL CLARK

Those who already exercise should continue their regular workouts, Comander says.

Jodi Monroe, 53, of Mount Vernon, Washington, was already an avid exerciser when she received a diagnosis of breast cancer — stage 3a triple-positive ductal carcinoma &mdash; at age 47. She had a mastectomy on her left side, followed by eight months of bio-chemotherapy and the placement of a skin expander to prepare for reconstruction. After facing an infection that required another emergency surgery, Monroe had 30 rounds of radiation, followed by a course of tamoxifen. She then began taking Arimidex.

“I never quit exercising, which probably has gotten me where I am,” she says. Still, the bone and joint pain she felt during her first year on the AI was debilitating. “I was at a business meeting, and I couldn’t even sit down,” she says.

After ruling out recurrence in the bone, her oncologist recommended acupuncture to help deal with the arthralgia. Monroe took part in a multicenter randomized clinical trial that compared the effects of true acupuncture, sham acupuncture (shallow insertion of needles at nonacupuncture points) and no treatment (the control group) on AI-related joint pain in women with early-stage breast cancer. The study, published in July 2018 in JAMA, found that women who received true acupuncture had less joint pain after six weeks compared with those in the sham and control groups.

Although Monroe doesn’t know which group she was assigned to — sham or real acupuncture &mdash; she has continued acupuncture treatments since the study ended. Previously, she was a naysayer regarding treatments like acupuncture and chiropractic care, she recalls. “I’d had muscle pain from weight lifting, but mainly, I’d just gut it out,” she says. “But I hadn’t experienced bone pain like this. With acupuncture, I’d see a huge difference in pain for a few weeks after treatment.”

Hershman, the study’s lead author, says that not only did participants who received true acupuncture have less pain after six weeks of treatment, they also had reduced joint stiffness — and those effects persisted throughout the 24-week intervention.

“Our goal as practitioners is to help patients stay on medications that are effective,” Hershman says. “Acupuncture has low toxicity and provides benefit to some. It gives us something different to offer to patients who are suffering.”

Heather Greenlee, N.D., Ph.D., a co-author of the study, medical director of the Integrative Medicine Program at Seattle Cancer Care Alliance and an epidemiologist at Fred Hutchinson Cancer Research Center in Seattle, said she expects to see an uptick in the use of acupuncture to help manage arthralgia. In May 2018, the American Society of Clinical Oncology endorsed the Society for Integrative Oncology’s evidence-based clinical guidelines on integrative therapies, including acupuncture, for managing symptoms and side effects of cancer and its treatment.

“We want to get this information (about acupuncture relieving arthralgia) into the hands of patients and clinicians,” Greenlee says. Those who want to try the technique should find an acupuncturist who is trained to work with oncology patients, she says, and can follow the study’s recommended point protocol 

. A list of the acupuncture points can be accessed at https://tinyurl.com/y7a6mmdb.

Acupuncture does have some potential drawbacks, Hershman adds. Some people are afraid of needles; others can’t afford the time or cost. Each session runs $60 to $120, on average, and might not be covered by insurance. Coverage for acupuncture treatments varies by state, as well as according to a plan’s particulars, Greenlee says.

“That’s one of the main reasons we did the study — to provide level one evidence” of acupuncture’s effectiveness, Hershman says, which could lead to more insurance coverage. Monroe’s plan covered a certain number of acupuncture sessions each year; after that, she paid out of pocket. “My health and comfort come first,” she says. Hershman urges others to follow Monroe’s lead.

Anyone taking AIs and experiencing arthralgia symptoms should talk to their oncologist. “Don’t stop taking your medication,” she says. She encourages all patients to exercise, unless there’s a reason they shouldn’t, and eat a healthy diet — it might not ease arthralgia but can help to both maintain a normal body weight and prevent recurrence. Those interested in acupuncture but worried about the cost can check with their cancer centers to see if there’s an acupuncturist on staff or seek a referral to one who offers reduced fees for patients with cancer. Acupuncture can also be found in a clinic environment, where a number of people are treated simultaneously at reduced rates. A list of clinics by state is offered by the People’s Organization of Community Acupuncture at pocacoop.com.

Monroe, who still takes Arimidex every day, credits exercise and acupuncture with helping her continue high-level athletic pursuits, including a 200-mile Seattle-to-Portland bike ride and training for a dragon boat competition in Hungary, where she competed in the Club Crew World Championships.

“Because I’m high risk, I’m going to stay on an AI for life,” she says, adding that her stage 3a diagnosis included a golf ball-size node in her armpit and seven additional positive lymph nodes. “But acupuncture, exercise, massage and a good attitude have gotten me through a lot.”

Exercise and acupuncture use the body’s physiology to relieve joint pain caused by hormonal treatments after breast cancer.

Flexing Some Muscle to Relieve Joint Pain

KARI WERGELAND'S new book is available at finishinglinepress.com and Amazon. - WERGELAND PHOTO BY IAN CUMMINGS

SO BEGINS KARI WERGELAND’S account of her recent illness and treatment, titled “Breast Cancer: A Poem in Five Acts.”

In her book, published this year by Finishing Line Press, Wergeland recounts her journey in just 32 pages, divided into five sections: Diagnosis, Surgery, Chemo, Radiation and Follow-up.

She shares recollections about the treatments she received, side effects she experienced, insights she had and steps she took to sustain her body and spirit, whittling the cancer experience down to a small collection of vivid milestone moments. Signs of life going on around her in San Diego County and in her dreams, and what they might symbolize — spiders, snakes, lizards &mdash; follow her through her story.

“I wasn’t writing the chapbook for therapeutic reasons; I decided early on it would be a serious piece of writing,” Wergeland recalls. “However, as I played with this work in progress, I had a number of aha moments on the spot.

More than once, the poem allowed me to understand something I hadn’t fully delineated in my conscious thinking: ‘Yes, this is how I’m really feeling!’ I found these insights interesting — and comforting.”

“A Poem in Five Acts” is an easy yet unique and insightful read for those living with breast cancer, who will find many relatable details within the pages. The tone is realistic but ultimately hopeful, revealing how Wergeland quietly perseveres through each stage of treatment despite fear and discomfort. Although the book can be read quickly, those moved by Wergeland’s insights are likely to pick it up again and again.

Bookshelf

In a new book of poetry, Kari Wergeland describes key recollections and insights from her journey with breast cancer.

Breast Cancer Special Issue | CURE