IT CAN BE DIFFICULT to fathom a cancer diagnosis, let alone even begin to think about the aftermath of the associated treatment. For many women, ending treatment is met with 

It’s crucial for health care teams to understand each woman’s bone health status and risk of fractures before deciding on a course of treatment. Although this is a major concern, there are strategies to achieve better bone health such as eating foods that are high in calcium or adding an exercise regimen to the daily routine.

, one of the features explores the different therapies that can play a role in bone health. Two patients share how they were affected following treatment and despite the challenges, they remained hopeful.

gestational trophoblastic neoplasia (GTN)

, which are a group of placenta-related cancers that can develop following pregnancy, miscarriage or abortion. These types of malignancies are rare and very curable, but can often be isolating to the women diagnosed. In these pages, you will hear from a woman who learned she had GTN after the tumors metastasized to her liver, lungs, kidney, pancreas and brain. After putting up the fight for her life, she is now in remission.

Saving lives involves bringing the best and latest available therapies to patients. One of the ways to do so is through clinical trials. However, enrollment of women with gynecologic cancers has decreased in recent years. The

 has brought the clinical trial crisis into the limelight. The foundation explains how it’s trying to eliminate the decrease through advocacy and awareness.

When clinical trials or other cancer-related studies present positive results, the data generally make its way to the mainstream media. The unfortunate result is news hype. Patients start to read headlines and stories that sound promising, but may actually be misleading or inaccurate. In the 

, a 20-year breast cancer survivor discusses a new program that ranks cancerrelated news articles. It helps patients identify potential hype by ranking news articles and putting clinical data into language that is more easily understood. In doing so, patients can be better informed to make decisions on their health.

Also in this issue, addressing sexual health concerns of patients and their partners, using blueberries to treat cervical cancer and seeing the new, better you after a cancer diagnosis. As always, thank you for reading.

Articles

From the Chairman

It can be difficult to fathom a cancer diagnosis, let alone even begin to think about the aftermath of the associated treatment. For many women, ending treatment is met with bone density issues, such as osteopenia and osteoporosis.

Finding Hope in Cancer's Aftermath

DESPITE THE MANY ADVANCES in cancer care in recent decades, one aspect that hasn’t seen much improvement is the detection of ovarian cancer in its earliest stages. Finding the disease sooner could have a big impact on survival compared with what is experienced with later diagnoses.

However, nonspecific symptoms usually impede prompt evaluation. For instance, bloating, feeling full quickly and pelvic pain — all early signs of ovarian cancer &mdash; are also associated with maladies that are less life-threatening. These symptoms may go unreported or even lead to misdiagnosis.

Researchers are investigating new and more sophisticated tests to help screen for the disease, because many of the existing tests are not that sensitive or specific. For instance, cancer antigen 125 (CA 125), a protein in the blood that is often found at high levels in women with ovarian cancer, has been found to not be useful because common conditions other than cancer can also cause high levels of CA 125 and not every woman with ovarian cancer has a high CA 125 level. However, researchers are now studying CA 125 in a different way using careful calculations of the change over time, or the velocity, which may be more accurate and effective for early detection. Although most ovarian cancers are found in advanced stages, there still have been improvements in treatment. Avastin (bevacizumab), which is a targeted therapy, continues to shrink or slow the growth of advanced epithelial ovarian cancers. More recently, excitement has built around

 These types of agents have proven to be effective in managing patients with epithelial ovarian cancer who have known mutations (germline or somatic) in the BRCA gene. PARP inhibitors are also proving valuable for some patients who don’t have BRCA gene mutations but may have other biological features that affect DNA repair (a key function of the BRCA gene).

, we feature an article on some of these new advances in ovarian cancer treatment, including neoadjuvant therapy — chemotherapy that is used to shrink a tumor before surgery. Neoadjuvant therapy may not only be a better way to treat patients but also provides a potential research platform to study new drugs and perform tissue-based correlative trials yielding results more quickly and efficiently than standard trials. You will read the stories of two women with advanced ovarian cancer who received neoadjuvant therapy. One also opted for a newer technique referred to as heated chemotherapy, and she wishes more women were aware of this post-surgery therapy that she considers lifesaving.

Nowadays, all patients with ovarian cancer receive genetic testing, which is crucial. Research has found that mutations in BRCA1 and BRCA2 account for around 15 percent of ovarian cancers overall. It’s important that patients be made aware of the available genetic testing by their health care team and offered it, regardless of family history. Often referred to as the silent killer, ovarian cancer doesn’t have to be that. We have high hopes that, with better detection in early stages, evolving treatments and disease awareness, steady improvements will translate into saved lives.

Chair, Department of Breast Medical Oncology 

The University of Texas MD Anderson Cancer Center

Editor's Page

Despite the many advances in cancer care in recent decades, one aspect that hasn’t seen much improvement is the detection of ovarian cancer in its earliest stages. Finding the disease sooner could have a big impact on survival compared with what is experienced with later diagnoses.

Eliminating the 'Silent Killer' in Gynecologic Cancers

WOMEN WITH VULVAR CANCERS who test positive for human papillomavirus (HPV) may have improved survival compared with HPV-negative patients, according to the results of a new study.

The meta-analysis involved 18 studies that included 1,638 women, ranging in age from their early 60s to early 70s, with vulvar cancers tested for HPV (541 positive and 1,097 negative). The researchers examined overall survival, disease-free survival, disease-specific survival and progression-free survival.

The researchers found that among women who were alive five years after their cancer was diagnosed, 50 to 86 percent were HPVpositive and 43 to 71 percent were HPV-negative. In addition, disease-free, disease-specific and progression-free survival pointed toward more favorable outcomes among women with HPV-positive vulvar cancers compared with HPV-negative, the authors concluded.

“This could be of great clinical interest and provides insight into the differences in the natural history of HPV-positive and -negative vulvar cancers,” they wrote.

Research News and Updates

Women with vulvar cancer who test positive for human papillomavirus (HPV) may have improved survival compared with HPV-negative patients, according to the results of a new study.

HPV Status Linked to Overall and Disease-Free Survival in Vulvar Cancer

FOLLOWING THE START of menopause, Karen Roberts was put on Arimidex and now has osteopenia. - PHOTO BY BOB RIVES

Karen Roberts of Washington, D.C., was 53 in 2009 when she was diagnosed with stage 2b breast cancer. Her tumor had both estrogen- and progesteronepositive receptors. In consultation with her doctors, she opted for a full mastectomy on one side, followed by 24 weeks of chemotherapy and six weeks of radiation.

Although many women go into menopause after treatment, Roberts remained perimenopausal — her body was making the natural transition to menopause. To prevent a recurrence of her cancer, Roberts began adjuvant endocrine therapy, also called hormonal therapy.

Since she was perimenopausal, her doctors prescribed tamoxifen, which is part of a class of drugs called selective estrogen receptor modulators. These drugs work by blocking estrogen’s effects in the breast, which helps slow the growth and reproduction of breast cancer cells. Although tamoxifen has many side effects — hot flashes, loss of sex drive, vaginal discharge and vaginal dryness or itching &mdash; it also has an estrogen-like effect on the bones, which has proven to be beneficial for postmenopausal women. Among these women, tamoxifen can improve bone density and help prevent osteopenia and osteoporosis.

Roberts took tamoxifen for five years. Once a year, she was given a bone density screening test to make sure her bones showed no signs of thinning. The treatment proved effective at both keeping the cancer at bay and maintaining her bone health.

Then Roberts went through menopause, so her treatment plan changed. For the past 2 ½ years, she has been taking Arimidex (anastrozole), an aromatase inhibitor that prevents the formation of the female hormone estradiol. Although Roberts remains cancer-free, the combination of becoming menopausal and taking Arimidex has taken its toll.

“My last bone density screening found that I now have osteopenia,” Roberts says. “I was really surprised, because I had been taking vitamin D and calcium to build up my bones. Also, I’m overweight, putting me at a slightly reduced risk. I don’t need any bone-protecting medications yet, but I do need to pay attention.”

Roberts is not alone. According to the National Osteoporosis Foundation, even within the general population, 1 in 2 women aged 50 years or older is at risk of a fracture due to osteoporosis in their lifetime. For postmenopausal women taking an aromatase inhibitor, the rate of bone loss increases from 1 percent to 2 percent each year. This small increase is enough to increase the risk of fracture.

THE ART AND SCIENCE OF TREATMENT MANAGEMENT

Knowledge about prescribed medications, their possible effects on the bones and how to address side effects offers the best defense against potentially devastating bone issues.

Bones are living tissue, and they continuously engage in formation and resorption. In healthy, young bones, these two processes are balanced. Problems arise when bone resorption exceeds formation. This often occurs with aging, and some medications can accelerate the process. Sometimes the result is osteopenia, or low bone mineral density. This mild to moderate thinning of the bone mass can progress to osteoporosis, a condition characterized by even lower bone mass, deterioration of bone tissue, disruption of the bones’ overall structure and an increased risk of fractures.

“The impact of cancer treatment on the bones varies by the type of cancer and its therapy,” says Catherine Hall Van Poznak, M.D., associate professor at the University of Michigan in Ann Arbor and an expert in bone health. “For example, cervical cancer is not an estrogen-sensitive tumor cell, so anti-estrogen therapy is not involved in its management, but women who have had radiotherapy may be at risk for bone fractures in the treated area. Endocrine therapy for uterine cancer is not well studied for bone health.

Premenopausal women who have had their ovaries removed experience premature menopause associated with a greater risk of osteoporosis. The largest group of women at risk for treatment-related bone loss are those with breast cancer. About 75 to 80 percent of this population have tumors fueled by hormones, so anti-estrogen treatments are used to prevent recurrence.”

The options available are tamoxifen, which is approved for both pre-, peri- and postmenopausal women, and aromatase inhibitors, including Arimidex, Aromasin (exemestane) and Femara (letrozole), which are effective only in postmenopausal women. Aromatase inhibitors are particularly deleterious to bones because of the affect they have on the levels of circulating estrogen that come from the adrenal glands, which makes androgen. The enzyme aromatase converts androgen to estrogen, but the aromatase inhibitors block the conversion from taking place. The effect of this treatment is to lower the amount of circulating estrogen.

Nonetheless, aromatase inhibitors are the treatment of choice for postmenopausal women with hormone-related, early-stage breast cancer, largely because of the findings from many studies comparing them with tamoxifen. For example, in 2005, a large clinical trial referred to as ATAC (Arimidex, Tamoxifen, Alone or in Combination), compared the effectiveness of the aromatase inhibitor Arimidex with tamoxifen among 9,366 postmenopausal women with localized breast cancer. The results showed that Arimidex compared with tamoxifen significantly prolonged diseasefree survival and time to recurrence, as well as significantly reduced local recurrences and distant metastases.

Although the study had a protocol that documented that bone loss was greater with Arimidex than with tamoxifen, it has taken widespread use of aromatase inhibitors to highlight the impact of these medications. Widespread use of aromatase inhibitors has revealed that these issues can be problematic and, over time, fracture rates clearly are higher with aromatase inhibitors compared with tamoxifen. In addition, joint pain is more common with aromatase inhibitors for reasons that are not well understood.

Given the biological profile of aromatase inhibitors, “it makes sense [that] we’re seeing more cases of fractures and osteoporosis,” notes Carolyn Crandall, M.D., M.S., a primary care physician and professor of medicine at the University of California, Los Angeles. “They are very potent drugs that bring estrogen levels way down.”

Deciding which therapy to use is “as much an art as a science,” according to Patricia Ganz, M.D., director of Cancer Prevention and Control Research at the UCLA Jonsson Comprehensive Cancer Center. “If a woman has good bones based on an initial bone density scan and has a large tumor with a higher risk of recurrence, aromatase inhibitors may be the right choice. On the other hand, if she is not tolerating the aromatase inhibitors well and is at low risk for blood clots, tamoxifen may work better. The goal is for women to stay on endocrine therapy for 10 years, so it’s essential to find one that they can tolerate over the long haul,” Ganz says.

Crandall agrees, adding that each woman is unique and should be carefully assessed based on her risk factors. “There’s no reason to think that every woman starts out with bad bone density or to jump the gun and assume that every woman is at an increased risk for fractures,” she says. “Some women are at a higher risk based on family history, parental history of hip fracture and body type, with slender women being at somewhat higher risk.”

Taking these factors into account helps determine how often to conduct scans, too. Crandall points out that women should stick with one facility for their scans. Each machine has its own idiosyncrasies, so getting scanned by the same one from year to year makes it easier to compare results accurately.

To help put all these pieces together, Crandall uses the Fracture Risk Assessment Tool (FRAX), a calculator developed by the World Health Organization Collaborating Centre in the United Kingdom and is recommended by clinical osteoporosis guidelines to determine whether a woman is at high risk of bone fractures. “It is helpful in making decisions about breast cancer treatment,” Crandall says.

The trajectory of Jennifer Morrison’s treatment plan illustrates the nuances involved in managing medications following breast cancer treatment. Diagnosed in 2013 with two different cancers in each breast, one at stage 1 and the other at stage 2, she opted for a double mastectomy and a full hysterectomy. The treatment put the then 44-year-old into menopause, so her oncologist, Julie Gralow, M.D., director of Breast Medical Oncology at Seattle Cancer Care Alliance, first tried Arimidex. When Morrison’s initial bone screening showed osteopenia in both hips, Gralow added infusions of Zometa (zoledronic acid), a bisphosphonate, once a year. These drugs not only help prevent bone loss but, according to results of recent studies, might prevent recurrences in postmenopausal patients with breast cancer. (For more information about the latest findings on the role of bisphosphonates in breast cancer treatment, see “Old Drug, New Tricks” in the CURE® October 2017 special issue on breast cancer.)

JENNIFER MORRISON developed joint pain and arthritis in her hands after taking Arimidex. - PHOTO BY SY BEAN

But Morrison soon experienced side effects from Arimidex. “I developed joint pain and arthritis in my hands,” she says. “In fact, one doctor said that my hands looked like they belonged to a 70-year-old, not a woman in her 40s. It was so bad that at one point I could barely hold a toothbrush.”

Gralow took her off Arimidex and put her on Aromasin. Since then, Morrison has noticed improvement in her hands. As for the infusions of Zometa, Morrison felt sick after the first one, but she and Gralow soon discovered that she did much better if the rate of infusion was slow.

With these adjustments, Morrison is moving better and has less joint pain. She has even started taking a Spin class — the high impact further supports her bones while on Aromasin.

Another option for patients is Prolia (denosumab), which may improve survival and cut the risk of bone issues. The drug was approved for the treatment of postmenopausal women with osteoporosis at high risk for fracture and to increase bone mass in women who may be at risk for fracture after adjuvant aromatase inhibitor therapy.

In addition to following an appropriate medication regimen, women can protect their bones by living a healthy lifestyle. For example, eating nutritious foods, including those high in calcium; drinking small amounts of alcohol; and not smoking.

Although the data are mixed about whether vitamin D and calcium supplements decrease the risk of fractures — the latest study from the Journal of the American Medical Association indicates that supplements don’t make a difference &mdash; the National Osteoporosis Foundation recommends that women aged 51 and older take 1,200 milligrams of calcium each day and that individuals aged 50 and older take 800 to 1,000 international units of vitamin D a day. Most clinicians agree and prescribe these supplements for their patients who do not consume these quantities in their diet.

Exercise, too, has known benefits for promoting bone health. In particular, weight-bearing exercises such as squats, lunges and stair-climbing help build bone density. “But any form of exercise can help improve balance, reduce fractures and minimize falls,” Gralow says. “Swimming and yoga improve muscle strength and coordination.”

Hawley Almstedt, Ph.D., an exercise physiologist and registered dietician at Loyola Marymount University in Los Angeles, conducted a small pilot study, Improving Physical Activity After Cancer Treatment, to determine the effect of an exercise program tailored for cancer survivors. The 13-week plan incorporated walking, core-strengthening moves and weight-bearing exercises. Although the study’s duration was too short to reveal widespread changes in bone density, many participants showed improvement in bone health at the femoral neck. A follow-up study that was twice as long showed significant improvements in bone mineral density throughout the body. These findings point to the potential of exercise in helping women improve their bone health.

“What I learned from both studies is that there is a general lack of awareness about bone health following cancer treatment,” Almstedt says. “There also is a need for more guidance on the types of exercise that work best for this population.”

Some women already have discovered how life-changing exercise can be. More than 20 years ago, a group of women cancer survivors in Seattle decided to participate in a triathlon and asked Gralow if she would serve as their physician. The experience had a profound effect on her, leading to the formation of Team Survivor Northwest, which helps women who are striving to make healthy lifestyle choices following cancer treatment. It also serves as a support group, where women meet other women, find an exercise partner or get help training for an event.

“I saw firsthand how empowering exercise was for women who had been through surgery, radiation and chemotherapy,” Gralow says. “Women start losing weight and feel better about their body image and themselves. They set manageable goals and succeed. I have seen amazing turnarounds in women’s lives.”

Features

Knowledge, physical activity and lifestyle changes can make a difference.

It's Complicated: Maintaining Healthy Bones Against All Odds

OVER MY 19-YEAR career in patient advocacy and as a 20-year breast cancer survivor, I have read my share of media reports on cancer research. I have learned to view the cycle of health media with skepticism. Too often, hope turns to disappointment as new discoveries fade from the media spotlight to obscurity.

Media reports of health news frequently contain misinformation and hype. This can be extremely confusing or dangerous for people who are making health care decisions. In her 2009 New England Journal of Medicine perspective, “Communicating Medical News — Pitfalls of Health Care Journalism,” health policy journalist Susan Dentzer wrote, “Journalists reporting on health care developments deliver public health messages that can influence the behavior of clinicians and patients.” She added, “I believe that when journalists ignore complexities or fail to provide context, the public health messages they convey are inevitably inadequate or distorted.”

As an organization supporting informed medical decisions for people and families affected by hereditary cancers, Facing Our Risk of Cancer Empowered, better known as FORCE, has observed the real-world consequences for consumers of health media hype and misleading stories on cancer research. Too often, headlines like “BRCA Gene Mutations Also Linked With Salivary Gland Cancer” or “‘Jolie Gene’ Linked to Alzheimer’s Disease” overstate the clinical significance of research and cause unnecessary concern or panic.

FORCE recognized an urgent need for tools to help people understand emerging research and discern if and how it affects their medical care. With funding from the Centers for Disease Control and Prevention, FORCE launched its eXamining the Relevance of Articles for Young Survivors (XRAYS) program in 2015. Using lay language to summarize media reports about breast cancer research, weekly XRAYS articles provide people with relevant context for their medical decision making.

Each XRAYS article evaluates and rates the relevance of the research to medical decisions and care. It also assesses the media’s coverage of the research, which may range from high-quality, five-star reporting to misleading or inaccurate coverage worthy of only one or two stars. All XRAYS articles are reviewed by a member of FORCE’s scientific advisory board before being published.

In an XRAYS blog, journalist Amy Wu wrote, “At a time when fake news is making headlines, programs such as XRAYS are all the more pivotal for patients, medical practitioners and yes journalists too…It sends a message out to media organizations that they are accountable for the information acquired and delivered.”

The XRAYS team recommends that people ask themselves the following questions to help critically evaluate health reports in the media:

Read the entire story. Sensational headlines may serve as click-bait, but sometimes a good article follows an erroneous headline.

Research on mice or cell lines is usually very preliminary. Even if the science is sound, it may be years away from testing in humans and incorporation into medical practice. For research in people, small studies usually require validation on larger populations before guidelines are changed. Also, consider if the participants share your medical situation. The more similarities between you and the population studied, the more relevant the results will be to you.

Balanced articles include quotes from experts outside the research team. This is important because many health media reports start with a press release that focuses on an institution’s contribution to science rather than the immediate impact on patient care. Visit the website of professional organizations such as the National Comprehensive Cancer Network, which has expert panels that review new research for incorporation into guidelines for care.

Many health media stories are based on research journal publications. Google the journal and researcher’s name to find the scientific article. Some may be technical, but reading the abstract can help you understand the investigators’ findings.

Share articles that you feel may affect your care or medical decision making with your doctor.

The media don’t always cover the most important stories. For hereditary cancer, many stories involve new drugs, genetic testing and Angelina Jolie. But research on topics such as long-term survivorship, metastatic cancer, quality of life and health equity do not receive much attention. Visit the United States Library of Medicine’s website, PubMed, to subscribe to alerts when articles are published on topics that interest you.

From discovery to incorporation into medical care, research can follow a slow, winding path with many years, headlines, false starts, contradictions and media reports in between. It’s worthwhile to arm yourself with resources like XRAYS to become an informed consumer of health media.

Visit FORCE’s XRAYS program at facingourrisk.org/ XRAYS

SUE FRIEDMAN was diagnosed with breast cancer 20 years ago at age 33 and subsequently learned that she carries a BRCA2 mutation. A veterinarian by training, Friedman founded the national nonprofit organization Facing Our Risk of Cancer Empowered (FORCE) in 1999 and left her practice several years later to serve as the organization’s full-time executive director.

Speaking Out

FORCES’s XRAYS program sorts through cancer research-related news to help patients make informed decisions.

Behind the Hype: Navigating Cancer News

THE SILENCE ON SEX and cancer is deafening. Although sex is a natural and important part of life, patients, survivors and partners don’t always feel supported in this area of treatment aftermath.

Recently, the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) issued updated guidelines on the subject. For women’s cancers, ASCO recommends that all oncology professionals offer psychosocial and/or psychosexual counseling, in addition to treatment for genital symptoms. The NCCN advises screening for physiological factors, such as menopause or illness; disease-induced changes; medication- induced side effects; and psychological factors. For nearly 40 years, Leslie Schover, Ph.D., a clinical psychologist and the founder of Will2Love, has helped patients overcome cancer-related concerns about sex and fertility.

, she provided answers to the questions that many are too embarrassed to discuss.

What are the most common sexual concerns among women who have been treated for gynecologic cancers?

Schover: The most troublesome is vaginal dryness, pain with caressing on the vulva and pain with penetration of the vagina, which often goes along with reduced vaginal size. They are concerned about anything that can cause premature menopause or — even for women who are already menopausal &mdash; worsen the symptoms. Loss of stretchiness of the vaginal area, loss of blood vessels and a more tender vulva can cause a lot of problems because of pain.

The second most common concern that women face is loss of desire for sex. But the first thing I ask when I hear that is “Are you having pain?” If sex hurts, you won’t look forward to it.

Some women are concerned about incontinence, either urinary or fecal, which can be embarrassing. It’s a really under-recognized problem.

How can women overcome these sexual challenges?

It’s important for women to be assertive and talk with their oncologist. If they don’t get a good response, they should talk with their gynecologist. It’s a real dilemma for women, because a lot of times community gynecologists don’t know a lot about cancer-related sexual problems.

A woman may regard her gynecologist as kind of the sex expert, but a lot are not knowledgeable about these problems. Sometimes it helps to look for a gynecologist who specializes in menopause.

One thing women can do right away, especially if they are experiencing pain, is try over-the-counter vaginal moisturizers and lubricants that don’t contain hormones.

Some of these products require daily use to be effective. I recommend that women use a combination of a vaginal moisturizer at bedtime three times a week, or up to daily if needed, and then add in a good water- or silicone-based sexual lubricant when they have sexual activity. They should spread it liberally on themselves and their partner. Even the best lubricants dry out after a few minutes, so instead of doing this secretly in the bathroom, make it part of lovemaking and foreplay.

A vaginal dilator, which stretches the vagina, is another option, although it’s best to consult a gynecologist to make sure it’s safe.

When is it safe to have sex again following a cancer diagnosis?

For most women, it’s OK at any time. There are a few exceptions, however. If a woman has a tumor, like a cervical cancer, with a lot of bleeding, then her oncologist may tell her to avoid sexual penetration until enough treatment has been given to reduce the extreme bleeding. Another problem: when the immune system is suppressed, such as during chemotherapy. Again, the oncologist may suggest not having sexual activity — or even avoiding other close contact with people &mdash; to lower the risk of infection. These are both usually temporary issues. A few chemotherapies also can cause temporary vaginal irritation. A person wouldn’t want to aggravate that by trying to have sex when she is hurting.

How can partners get involved, and how can single women who are dating handle this?

When a woman is in a close relationship, the more she and her partner talk, the better off they’ll be. It’s best to discuss it before being in the bedroom, because that’s when both people are most vulnerable. Find a private time and say, ‘There is some stuff I’d really like to talk about.’ If it’s difficult to talk with one another, that may be a great reason to see a counselor, who can offer a safe space.

For women who are single, dating is a challenge in general. After cancer, people always ask: ‘When should I tell a new partner about my cancer? Should I tell a partner about my cancer history?’ I think one common mistake people make is blurting it out immediately. Get to know the person and get a sense of their friendliness before bringing up the illness or any limitations on your sex life.

The other extreme mistake is to try to hide it, and then have someone find out and feel really insulted or betrayed. The one reassuring thing that I try to always say is that if someone rejects you because you have had cancer, you wouldn’t really want to have that person in your life.

How can women regain their sexiness when they may feel less attractive?

It’s a learning process and requires practice. I often suggest that women practice looking at themselves in the mirror. They should start out completely dressed and wearing their usual makeup, then identify three things that they like about the way they look. When they can do that, they should do the same wearing just a bathrobe and no makeup. Finally, they should look at themselves in the nude and still make those positive affirmations.

There are plenty of myths about sex and cancer. Which ones would you like to bust?

One of the big ones is that cancer is contagious through sex. People get confused partly because there are a few types that are related to the human papillomavirus, which is sexually transmitted. But it’s the virus that is transmitted, not the cancer.

Then there is the myth that having sex will make cancer worsen or return. Sometimes women, especially those who are less educated, worry that caressing breasts leads to breast cancer, and there are no relationships there.

Expert Leslie Schover, Ph.D., offers advice &mdash; that really works &mdash; on sex after cancer treatment.

Let's Talk About Sexual Intimacy

SUSAN BALDRIDGE has no evidence of disease, but still experiences side effects of chemotherapy. - PHOTO BY TAMZIN SMITH

When Susan Baldridge, 62, saw her primary care doctor for some ongoing stomach issues, she never expected that a few days later, she would receive this diagnosis: stage 3c ovarian cancer.

“My primary care doctor told me that if my issues continued or if I ran a fever, to go to the emergency room,” Baldridge recalls. “That is exactly what happened on January 27, 2017, and that is where they told me they found a mass on my ovary.”

The emergency room physicians described the mass as typical of ovarian cancer and began working on Baldridge’s transfer to Inova Fairfax Hospital’s women’s clinic in West Falls Church, Virginia. There, she would receive more specialized treatment.

This year, more than 22,000 women — roughly half aged 63 years or older &mdash; will receive a diagnosis of ovarian cancer, the fifth leading cause of cancer death in women. “One of the biggest challenges of ovarian cancer is early diagnosis,” says Thomas J. Herzog, M.D., deputy director of the University of Cincinnati Cancer Institute and a professor of obstetrics and gynecology at the College of Medicine. “Almost three-quarters of women will present with advanced stage disease, meaning the disease has spread beyond the ovaries and pelvis at the time of diagnosis.”

Diagnosis of ovarian cancer tends to be late because the symptoms — bloating, pelvic or abdominal pain, feeling full quickly, urinary symptoms, fatigue, back pain and constipation &mdash; are vague and often do not occur until the disease has already spread, Herzog says. “The problem is, a lot of other conditions can cause those symptoms too,” he adds.

Screening tests for ovarian cancer have not been as successful as mammography and colonoscopy, which can help detect breast and colon cancer, and there is no validated screening program for the general population.

For those at increased risk, two tests are available: transvaginal ultrasound and the cancer antigen (CA) 125 blood test. A transvaginal ultrasound looks for masses in the uterus, fallopian tubes or ovaries, but it cannot distinguish between a cancerous or noncancerous mass. The blood test helps detect high levels of CA 125, a protein that is often elevated in women with ovarian cancer; however, other common health conditions also can cause CA 125 to rise. Because these tests are not very accurate, they can lead to many false alarms, especially with borderline CA 125 elevation, as well as missed cancers.

A large increase in CA 125 created concern for Joanna Gutermuth, 42, of Lutherville, Maryland. At age 32, prompted by a family history of breast cancer, she had undergone genetic testing. “My aunts all had breast cancer, and my mom was an ovarian and breast cancer survivor,” Gutermuth says. “I knew the odds were against me.”

Hereditary breast and ovarian cancer syndrome, associated with mutations in the genes BRCA1 and BRCA2, is linked with a high risk of breast and ovarian cancer. The two genes are responsible for most inherited ovarian cancers: 39 percent of women who inherit a BRCA1 mutation and 11 to 17 percent of women who inherit a BRCA2 mutation will develop ovarian cancer by age 70, according to the National Cancer Institute.

Gutermuth’s genetic testing revealed that she was BRCA1-positive. In 2010, she had a prophylactic mastectomy to remove her breasts and reduce her risk of breast cancer. She also began monitoring her ovaries with ultrasound and checking her CA 125 levels every six months.

“When the CA 125 levels increased, I met with my husband and family, and decided to go ahead and have a prophylactic oophorectomy with hysterectomy,” Gutermuth says. “When I woke up from that procedure, the doctor told me I had cancer everywhere.” She received a diagnosis of stage 3c disease. TURNING UP THE HEAT For most women with advanced ovarian cancer, treatment entails surgery. The goal is to treat, stage and remove, or debulk, as much of the tumor as possible.

After making a small incision, the surgeon inserts a scope to make sure the disease can be removed to less than 1 centimeter. This is called optimally debulked, according to Bhavana Pothuri, M.D., a gynecologic oncologist at New York University Langone Health. “Once that is determined, we make a large incision and remove the uterus, cervix, fallopian tubes and ovaries,” Pothuri says. “We also remove the layer of fatty tissue covering the abdominal contents, and, in some cases, we may also need to remove part of the bowel, bladder or spleen.”

These procedures can be long and intensive, she adds, and often require three to seven days’ hospitalization. “It is aggressive, but we do it to be as sure as possible that we get as much of the disease out as we can,” Pothuri says.

Before undergoing primary debulking surgery, both Gutermuth and Baldridge received chemotherapy, an approach called neoadjuvant therapy — a step to shrink a tumor before main treatment.

“Giving chemotherapy prior to surgery is increasingly an exception to the standard of care,” says Maurie Markman, M.D., president of medicine and science at Cancer Treatment Centers of America. “This doesn’t mean a patient is denied surgery. Performing surgery after chemotherapy leads to similar outcomes but with reduced morbidity, less disease and an easier operation.”

The international CHORUS trial compared outcomes in women with suspected stage 3 or 4 ovarian cancer. They were randomly assigned to receive either primary surgery followed by six cycles of chemotherapy, or three cycles of primary chemotherapy followed by surgery and another three cycles of chemotherapy. Survival outcomes between the two groups were similar, but women who underwent primary chemotherapy experienced fewer serious postoperative side effects and deaths.

Baldridge received nine weeks of chemotherapy with carboplatin and Taxol (paclitaxel), both before and after her debulking surgery. “My doctor felt that we could be more successful if we did half of the chemotherapy first, and then, after surgery, hit it again with more chemotherapy to make sure that cancer cells weren’t hiding anywhere else,” Baldridge says. “I trusted him completely.”

Gutermuth also underwent neoadjuvant, or preoperative, chemotherapy, but after her procedure, she received hyperthermic intraperitoneal chemotherapy (HIPEC), also known as heated or hot chemotherapy. HIPEC is given as a single treatment in the operating room after all visible tumors are removed. The solution is heated to between 107.6 and 109.4 degrees Fahrenheit to kill any remaining cancer cells and preserve the healthy ones. It is delivered directly into the abdomen — making it ideal for a patient whose disease is confined to the body cavity &mdash; for about 90 minutes.

Gutermuth spent one night in the intensive care unit and 12 days in the hospital. “The recovery was pretty intense but worth it,” she says.

Because the procedure can be associated with major side effects, HIPEC is not widely used. Although data support potential clinical benefit, it remains uncertain if similar favorable outcomes would be observed with strategies that are considerably less likely to result in serious toxicity, Markman explains.

Risks involved in HIPEC include bleeding, infection and, less commonly, blood clots in the legs. Because it can be challenging to consume enough calories as the digestive system recovers, patients may need to receive nutrition intravenously or through a feeding tube. Any residual scarring in the peritoneal cavity can result in chronic pain and altered bowel function.

During a recent trip to Camp Mak-A-Dream, a retreat for cancer survivors in Gold Creek, Montana, Gutermuth was surprised to learn that of the 48 women she spoke with, just two had even heard of HIPEC. “I tried to talk to them about HIPEC and how incredible it was for me — it was lifesaving,” she says.

In a recent study conducted in the Netherlands, investigators compared the use of HIPEC with cisplatin with surgery alone in 245 women with stage 3 epithelial ovarian, fallopian tube or peritoneal cancer. Women who received HIPEC had longer recurrence-free survival and overall survival compared with those who did not receive HIPEC, and the heated chemotherapy did not significantly increase side effects. “Once a literature search supports the results of this trial, we will want to implement (HIPEC) as a standard of care,” says lead study author Willemien J. van Driel, M.D., Ph.D., of the Netherlands Cancer Institute in Amsterdam. “It will be difficult to repeat this trial with this number of patients, and the results are convincing.”

Unfortunately, regardless of which initial treatment is selected, 70 to 90 percent of women diagnosed with advanced ovarian cancer have a recurrence, according to the Ovarian Cancer Research Fund Alliance. If the disease recurs within six months of chemotherapy, it is classified as platinumresistant; if it recurs after six months, it is platinum-sensitive. The disease’s classification may affect which additional treatments can be tried.

After undergoing a second round of HIPEC for disease recurrence, Gutermuth is continuing maintenance treatment with Avastin (bevacizumab), a targeted agent designed to attack the blood vessels that grow and support the tumor. She receives infusions every three weeks and has regular scans every three months to make sure the disease has not returned.

Avastin was first approved by the Food and Drug Administration (FDA) in 2014 in combination with chemotherapy for women with platinum-resistant recurrent epithelial ovarian cancer after a phase 3 clinical trial showed a 62 percent reduction in the risk of disease worsening or death compared with treatment with chemotherapy alone. In 2016, the FDA approved Avastin combined with chemotherapy for women with platinumsensitive disease.

One of the newest, most exciting areas of development in targeted therapies has been PARP inhibitors, according to Pothuri. “These inhibitors work particularly well in women with BRCA-positive disease,” she says.

The first PARP inhibitor, Lynparza (olaparib), was approved by the FDA in 2014 for patients with a BRCA mutation, who had been treated with three or more prior therapies. In these patients, Lynparza almost tripled the amount of time before their disease progressed. In August 2017, the FDA expanded the drug’s use to include maintenance treatment of patients who are in complete or partial response to platinum-based chemotherapy.

In 2016, the FDA approved a second PARP inhibitor, Rubraca (rucaparib), for women with ovarian cancer with a germline or somatic BRCA mutation who had at least two prior therapies. The results of a clinical study of Rubraca showed that about 80 percent of women with a BRCA mutation responded to therapy.

Most recently, in March 2017, the FDA approved Zejula (niraparib) for maintenance therapy in woman who have achieved complete or partial response to second-line treatment with a platinum-based chemotherapy, regardless of mutation status. A trial of Zejula showed that in women with BRCA-positive disease, the median time of progression- free survival was 21 months compared with just 5.5 months for placebo.

“PARP inhibitors are exciting and are a nice addition to our treatment options for these women,” Herzog says.

More than a year after receiving her diagnosis, Baldridge has no evidence of disease. Although she experiences some side effects from chemotherapy, such as chemo brain, she is grateful for each day. “It is amazing what the human body can go through,” Baldridge says. “I do not know why I did so well or why my prognosis is so good, but I attribute it to my great care team and the power of prayer.”

When talking with other women diagnosed with ovarian cancer, Baldridge stresses the importance of gathering as much information as possible, and Gutermuth could not agree more. She credits the use of HIPEC, something she had never heard of before her cancer journey, with saving her life. “I am not as active as I used to be, but I still paint and read, and mentor other women with ovarian cancer,” she says. “Every day is a blessing.”

Oncologists explore neoadjuvant therapy, heated chemotherapy and PARP inhibitors to find the right treatment for women with ovarian cancer.

Leaving No Stone Unturned in Ovarian Cancer

CINDY LUPICA was diagnosed with choriocarcinoma four months after giving birth to her daughter. - PHOTO BY SHARON WALLACE

In September 2013, Cindy Lupica, then 37 years old, gave birth to a healthy baby girl. The scene was dramatic, much like Lupica feared it would be. She delivered at 39 weeks in the ambulance on the way to the hospital. Her rural, Mojave Desert home near Apple Valley, California, is a half hour from the nearest hospital.

When Lupica started having contractions at 25 weeks, she began to worry that the birth would be quick and she wouldn’t make it to the hospital. With her three previous pregnancies, Lupica hadn’t experienced contractions so early on. But she had two normal ultrasounds, and her doctor wasn’t terribly concerned. “He asked if I was exercising and told me to maybe cut back a little,” Lupica recalls.

For six weeks after her daughter’s birth, Lupica bled. Again, that hadn’t happened with her other pregnancies, but again, her doctor was not alarmed. He suggested it was caused by hormones because this time, she was an older mom. Finally, the bleeding stopped, followed by intermittent spotting — until one night in late January, she began to hemorrhage.

By the time Lupica saw her OB/GYN the next day, the bleeding had stopped, but an ultrasound revealed what looked to her like a bunch of grapes in her uterus. The doctor had an idea what it was, but because Lupica didn’t have health insurance at the time, he sent her to the emergency room (ER) at a public hospital. He knew she could get affordable care, a diagnosis and treatment there.

When she arrived at the ER two days after the initial hemorrhaging, Lupica started to bleed more profusely again. The ER staff were sure she was having a miscarriage and moved her to labor and delivery. Lupica insisted that she wasn’t miscarrying, explaining that she’d had a baby four months earlier and had intermittent bleeding ever since. Lupica filled two buckets with blood that day. When the doctor got in to see her, he ordered a human chorionic gonadotropin (HCG) test “stat,” she recalls. Lupica knew she was in trouble. “They drew my blood, and within half an hour, we had three or four doctors come in and tell us the news.”

HCG is what creates a positive result on a home-pregnancy test. When a fertilized egg implants in the uterus, the placenta produces the hormone, which is detectable in the urine just days later. But if HCG is still in the body more than three weeks after giving birth, it can be a sign of a problem, including one of several placenta-related cancers, collectively known as gestational trophoblastic neoplasia (GTN).

GTN refers to several types of rare tumors that grow out of the placenta. That is, they grow out of a layer of cells called trophoblasts, which normally give rise to the placenta during pregnancy. GTN tumors can be highly prone to metastatic disease if not caught early, but remarkably, they are exceptionally responsive to chemotherapy and can be cured, even at advanced stages. For those few women who don’t respond to chemotherapy, immunotherapy drugs bring new hope.

The most common form of GTN, occurring in about 1 in 1,000 pregnancies, is a complete or partial molar pregnancy. A complete mole usually occurs when one or two sperm cells fertilize a so-called empty egg — it doesn’t contain DNA. Because the only genetic material comes from the father, fetal tissue does not develop. In a partial molar pregnancy, two sperm fertilize a normal egg. A tumor develops out of a combination of trophoblastic and fetal tissue, but a viable fetus doesn’t form. When detected early, moles are often confined to the uterus and not malignant. The prognosis of cure for those tumors (sometimes referred to as gestational trophoblastic disease, or GTD) is excellent.

“Doctors might detect molar pregnancies in several ways,” says Elisabeth Diver, M.D., a gynecologic oncologist at Stanford Health Care in Palo Alto, California. “An early pregnancy ultrasound could reveal the abnormality. A woman could have abnormal HCG levels. Or, particularly in the case of a partial mole, a woman might require a suction evacuation [dilation and curettage (D and C)] after a miscarriage, and the pathology will indicate that it was a mole.”

In most cases, moles can be entirely removed with a D and C. After the procedure, doctors monitor a woman’s HCG for up to a year to make sure it stays at prepregnancy levels, which indicates the molar tissue was completely removed and none continues to grow in the uterus. “If you’ve had just one molar pregnancy, you’ve been monitored preferably for up to a year, and everything is fine, there is no reason why you should not be able to attempt to get pregnant again,” Diver says. “However, it is critical that if you do become pregnant, you see an obstetrician very early on to check on ultrasound and make sure everything is normal.”

For many women, this frightening and lonely diagnosis follows the loss of a pregnancy. “There’s a lot of fear and guilt around wanting to be pregnant and getting pregnant again,” Diver says.

In rare cases, it’s possible to have a D and C and the HCG goes down, and then it starts to rise again, according to Don Dizon, M.D., director of women’s cancers at Lifespan Cancer Institute and of medical oncology at Rhode Island Hospital in Providence. “When that happens, we worry it has become invasive,” he says. Invasive moles, also called post-molar GTN, are just one of the more worrisome forms of GTN with metastatic potential.

For fewer than 1 in 5 women who has a complete molar pregnancy, the mole spreads beyond the lining of the uterus and into the muscular wall and cannot be removed by a D and C. In extremely rare cases, a partial mole can become invasive, as well. Post-molar GTN can spread to other organs — most often the lungs, which happens about 4 percent of the time.

Choriocarcinoma, the most aggressive form of GTN, is a tumor that can grow quickly and spread to other organs, including the brain, lungs and vagina. About half of cases follow molar pregnancy, and a quarter develop after miscarriage or abortion. The other quarter are the result of tissue that remains in the uterus after childbirth. Choriocarcinoma follows 2 to 7 of every 100,000 pregnancies in the United States.

Prolonged bleeding after a molar pregnancy, miscarriage or normal birth is the most common symptom of post-molar GTN or choriocarcinoma. Women might also have abdominal swelling. Choriocarcinoma that has spread to the lungs can cause a cough, difficulty breathing or chest pain. In the brain, it can cause headaches and dizziness.

CHEMOTHERAPY AND IMMUNOTHERAPY FOR PERSISTENT DISEASE

The night Lupica went to the hospital, the doctors told Lupica she had choriocarcinoma and admitted her. “All through the night and the next day, there were tests,” she says, “and they found that it had spread to my right lung.” The day after that, she started chemotherapy with methotrexate.

For women with GTN, curative treatment requires chemotherapy. Because the treatment usually works regardless of the size or stage of the cancer, patients are generally treated based on World Health Organization (WHO) risk score, Diver says.

“The key point is that someone with stage 4 choriocarcinoma can still be cured,” Dizon adds.

WHO risk score considers the following: age (over 40 is a higher risk than under 40); type of preceding pregnancy (a full-term birth is riskier than a molar pregnancy, a miscarriage or an abortion); time between pregnancy and diagnosis (sooner is better); HCG level (lower is better); tumor size, site of metastasis and number of metastases found; and whether the disease has already failed to respond to chemotherapy.

“Based on that score, the disease is either low-risk or high-risk,” Diver says. “Patients with low-risk disease get single-agent chemotherapy, and those with high-risk disease get multiagent.”

Lupica started with four weekly rounds of methotrexate, but her HCG levels continued to rise. She was resistant to the single agent, so her oncologists switched her to a multidrug regimen, which included etoposide, methotrexate and actinomycin-D, followed a week later by cyclophosphamide and Oncovin (vincristine), commonly referred to as EMA-CO. Finally, her HCG levels began to fall to those of a nonpregnant woman.

Today, Lupica is cancer-free. “I’m doing really well,” she says. “I have been blessed.” A testament to her health, she’s back to the demanding work of homeschooling her four children. But she continues to live with some of the side effects of such an aggressive regimen of chemotherapy: fatigue, neuropathy and some hearing loss.

Almost all low-risk and more than 80 percent of high-risk cases of GTN are curable with chemotherapy. But about 25 percent of women with high-risk disease become resistant to chemotherapy or relapse following treatment. For them, immunotherapy may bring another option.

This was the case for Melody Ransome, who didn’t know she had choriocarcinoma until 2 ½ years after giving birth to her son. She was 39 years old. By then, the tumors had metastasized to her liver, lungs, kidney, pancreas and brain. In retrospect, she recalls the warning signs of a persistent cough and a swollen abdomen.

MELODY RANSOME is in remission, but is monitored by monthly urine samples and annual checkups. - PHOTO BY DAVID WOOLFALL

Still, the doctors at Charing Cross Hospital in London, where Ransome lives, were undaunted. “They showed me the 7-centimeter tumor in my uterus and said, ‘We know what this is, and we can treat it,’” she recalls. After chemotherapy, Ransome went into remission, but she suffered two relapses over the next two years. The cancer progressed through five different chemotherapy regimens, two stem cell transplants and the removal of one-fifth of her left lung. That’s when her oncologist tried the monoclonal antibody Keytruda (pembrolizumab), an immunotherapy agent that helps the body’s own immune system attack and kill cancer cells. An experimental treatment for choriocarcinoma, Keytruda is approved by the Food and Drug Administration to treat several other cancers, such as advanced melanoma, advanced non-small cell lung cancer and classical Hodgkin lymphoma. After the second infusion, Ransome’s HCG level had dropped by 50 percent.

“That was the moment I knew it was going to work,” she says. “In two months, I was in remission and have been ever since.” That was more than two years ago.

While Ransome didn’t experience serious side effects from Keytruda, she still deals with side effects of EMA-CO, including tinnitus and neuropathy. Doctors continue to monitor her HCG through monthly urine samples and see her for annual checkups.

In the United States, researchers are currently recruiting women with persistent gestational trophoblastic disease for clinical trials to test several other monoclonal antibody drugs. “We are starting to see case reports of incredible results in patients who did not respond to chemo,” Dizon says.

In extremely rare cases — most often after a normal pregnancy or abortion, but possibly after a molar pregnancy &mdash; a placental-site trophoblastic tumor can develop in placental tissue that then attaches to the lining of the uterus. This happens about once in every 100,000 pregnancies. Even more rare, epithelioid trophoblastic tumors can grow in the uterus or cervix. These cervical tumors can be misdiagnosed as cervical cancer. “These are incredibly rare,” Diver says. “Unlike other forms of GTN, these tumors don’t respond well to chemotherapy, and frequently, hysterectomy is recommended, unlike with the other types.”

When a woman is diagnosed with GTN, odds are she doesn’t have a girlfriend, sister or aunt who’s been through it. “‘Choriocarcinoma,’ ‘placental trophoblastic disease’ — these were words I’d never heard before,” Ransome says. Lupica didn’t know other women who’d had the disease, either. She started her own online support groups. “They’ve helped me heal,” she says. “And now, girls are pouring in from all around the world, and they’re getting the support they need.”

Pregnancy can lead to a rare cancer known as gestational trophoblastic neoplasia.

Women's Cancers 2018 | CURE