A common, but not often talked about, side effect of mastectomy is post-mastectomy pain syndrome (PMPS). This type of chronic nerve pain, which can feel like burning, aching or shooting pain, may affect more than 50% of patients after mastectomy and breast surgery.

In the worst cases, PMPS can be extremely debilitating and damaging to people’s lives, resulting in an inability to work, the need for regular pain injections and chronic narcotic use.

In past years, when concern was predominantly about patient survival, pain was often ignored by the medical community. Patients were frequently told it was normal, would go away on its own or was “in their heads.” This mentality is shifting as more focus is rightfully placed on quality of life — and as surgeons learn more about nerve damage. Furthermore, advancements in modern medicine can now help mitigate and reverse post-mastectomy pain.

If you are experiencing chronic pain post-mastectomy that lasts longer than three to six months and you’ve tried physical therapy, pharmacological pain management and regional anesthesia, you may have nerve pain and/or a neuroma (a tangled mass of nerve endings and scar tissue) and could be a candidate for reparative surgery.

During a mastectomy, nerves that run toward the armpit area and the inner and outer chest are sometimes cut, stretched or pulled. With some mastectomies, nerves in the collarbone area can also be affected.


While cutting nerves is an inevitable and necessary part of surgery, because of the important role they play in the body it can be problematic
if they aren’t managed adequately. Peripheral nerves relay information between your brain and your body that allow you to move and feel. When cut nerves aren’t managed or repaired, they may grow uncontrollably and turn into a painful neuroma.

After nonsurgical options to treat PMPS have been exhausted, surgical intervention may be considered. If trigger points are found on physical exam that have not responded to other treatments, there may be trapped or damaged nerves that are generating constant pain.

There are a variety of surgical options for the treatment of entrapped, damaged nerve endings. Initial steps include surgical identification of the problem site, release of the nerve and removal of the abnormal nerve ending or scar until a normal, healthy segment is reached. Next, the fresh nerve ending is managed either through reconnection to another healthy nerve or to a nerve allograft, using a special nerve cap or replantation into surrounding body tissue or muscle.

It’s important to note that if a neuroma is simply removed and nothing is done to manage the nerve, another neuroma can form and the pain can come back; this can happen as early as three to six months post-surgery. When nerves are properly addressed, pain relief can be instant — even as nerves heal and regenerate. It’s also important to keep in mind that every person is different and that nerves are some of the slowest-regenerating tissues in the body, growing approximately 1 millimeter per day.

If you haven’t undergone breast surgery yet, here are some questions you should ask during your preoperative appointments with breast surgeons and plastic reconstructive surgeons (preferably, who work together as a team) to help you learn more about their experience in this area: If you’ve already had a mastectomy or breast surgery and believe you may be experiencing PMPS, consider asking your plastic reconstructive surgeon if you should see a pain specialist, if physical therapy could help or if you should consider surgical options. If you’re experiencing chronic pain in an area that was previously affected by breast cancer, an appropriate oncologic workup should be conducted.

Given the negative impact PMPS can have on quality of life, and its prevalence, all patients should be treated as if they are at risk for developing it.

It’s imperative for patients and providers to be aware of both the preventive and treatment options available. I believe that no matter how perfect a breast reconstruction looks, it’s successful only if the patient is pain free.

For more news on cancer updates, research and education, don’t forget to 

Articles

More than half of patients may experience PMPS, a type of chronic nerve pain, following mastectomy and breast surgery.

Post-Mastectomy Pain Syndrome: What Patients Need to Know

Oncology and technology are rapidly advancing and evolving every day — and in this 

, we give a look at what happens when those two worlds collide in unprecedented ways.

Artificial intelligence, also known as AI, has quickly become a hot-button topic. Its technological developments display the potential to transform nearly every aspect of our lives, including health and wellness.

One software engineer and cancer survivor tells us how she used the popular AI chatbot ChatGPT to tally up her medical expenses. Another survivor describes how an 

 helped her connect with a clinical trial.

But a number of oncology and technology experts we spoke with also urged caution.

AI platforms “are unique in that sense that they have amazing strengths, but they also have pretty important weaknesses, that, if you’re going to be using these things regularly, it’s important to know about,” Dr. Matthew Lungren says. Lungren is an associate clinical professor at the University of California, San Francisco, and chief medical information officer at Nuance Communications, a conversational AI company purchased in 2022 by Microsoft.

Elsewhere in this issue of CURE, we provide insight into the latest advancements in 

treatments for patients with ovarian cancer

 and look at the challenges faced by patients who are co-managing cancer and diabetes.

We are also working to keep patients with cancer up-to-date, both in print and online via 

, on the drug shortage that has affected the supply of certain cancer therapies.

“(Patients) should know that physicians and practices are scrambling, doing the best they can to manage this crisis,” said Dr. Lucio N. Gordan. “Patients and families need to connect with their representatives in Washington, D.C., to raise awareness and increase the level of urgency to improve channels of importation and to fix how these drugs are priced to allow them to stay viable from a financial and production standpoint.”

Also in this issue, we look at the potential benefits of 

 for patients with cancer, put a spotlight on the psychosocial issues faced by childhood patients and their families, and more.

As always, we hope you find our stories inspirational and informative. Thank you for reading.

Look Who's Chatting: Examining the Use of AI in Oncology

We are all used to shortages of a wide variety of commodities. They may seem more acute in recent times because of the sheer volume of materials being produced, shipped and consumed by the growing number of individuals joining the global economy. Coupled with more recent disruptions in supply chains due to worker shortages related to COVID-19, people leaving the workforce and myriad other factors, shortages can erupt and also resolve quickly. 

Cancer drugs are no exception to this phenomenon, despite their critical importance.

More CURE® coverage of the chemotherapy shortage:

Patients Respond to the Ongoing Chemo Drug Shortage

Here’s How One Cancer Center Is Handling the Chemo Shortage

Chemo Drug Shortage Requires a ‘Holistic Solution’

Expert Discusses Chemo Shortage: ‘Likely to Last’ 3 to 4 Months

Expert Identifies Chemo Shortage as a 'Simple Tragedy of US Health System’

Currently, the Food and Drug Administration (FDA) lists 119 drugs as being in short supply, including 25 cancer drugs, noting that definitions of shortages vary and that the degree of shortage can shift quickly. 

Among the notable drugs in short supply are the platinum-containing agents carboplatin and cisplatin — compounds that are able to bind to and crosslink DNA to inhibit its division and impede cell growth. The drugs are used for several cancer types and may not always be easily substituted. How do oncologists deal with chemotherapy drug shortages? General guidelines are being developed and modified, but they are based on several principles that include first looking for a substitute that is proven to yield somewhat equal therapeutic results. 

Also, doctors should prioritize a drug’s use in situations where the impact is greatest, such as offering a chance to cure a patient or increase their survival. There may be situations where dose or length of treatment modifications can be done safely — again, based on actual clinical data and not just conjecture. Many cancer centers and practices are adopting their own processes and guidelines for cancer drug shortages; patients may want to inquire about these with their care team if they are on treatment.

Additionally, the FDA has provisions that can be exercised in some situations, such as extending drug expiration dates — some of which are arbitrary — or when stability of the drug is known due to its chemical structure. Accelerat- ing approvals of new production lines or relaxing import rules for medicines that may be available elsewhere also may help. 

In addition, there is a focus on preventing or anticipating shortages. Companies are required to inform the FDA of impending production interruptions, issues that may affect availability or product integrity, and any disruption in shipping and distribution. Pharmacies and hospitals are also expected to maintain healthy inventories, while being aware of expiration dates.

Altogether, it is a shared responsibility by the pharmaceutical and health care industries to prevent, be prepared for and manage cancer drug shortages if and when they occur. The expansion of the cancer pharmaceutical/biotechnology sectors is reassuring not only in the sense that more effective and safer drugs are being developed, but that there may be more options if supplies become hampered.

Professor of Medicine Chair, Department of Breast Medical Oncology
The University of Texas MD Anderson Cancer Center

Currently, the Food and Drug Administration lists 119 drugs as being in short supply, including 25 cancer drugs.

The Shared Responsibility to Prevent, Prepare For and Manage Drug Shortages

CURE asked ChatGPT itself to write an article on the benefits of ChatGPT and artificial intelligence for patients with cancer and survivors. Here's what it "told" us. 

Transforming Cancer Care: The Empowering Potential of ChatGPT for Patients and Survivors 

Cancer, a formidable adversary that affects millions worldwide, not only takes a physical toll but also challenges the mental and emotional resilience of patients and survivors. Amid this battle, the advent of advanced technologies brings a ray of hope in the form of AI-powered solutions like ChatGPT, which hold the potential to significantly enhance the quality of life for those affected by cancer.

At its core, cancer care is a multidimensional journey that demands personalized support and information. ChatGPT’s capabilities to understand context, communicate empathetically and provide accurate information make it an ideal companion for patients and survivors. From deciphering complex medical terminology to explaining treatment options in a comprehensible manner, ChatGPT bridges the gap between medical expertise and patient understanding.

Can We Talk? Artificial Intelligence in the World of Cancer Care

The emotional toll of cancer cannot be understated. Patients often grapple with anxiety, depression and feelings of isolation. Here, ChatGPT steps in as a nonjudgmental confidant, offering a platform to express emotions without reservation. Through conversation, patients can find solace, share concerns and receive coping strategies to navigate their emotional rollercoaster.

Survivors, while victorious, often face post-treatment challenges and concerns about recurrence. ChatGPT’s accessibility empowers survivors to access post-treatment guidance and answers to pressing questions at their convenience. This not only fosters a sense of control but also aids in fostering a healthier survivorship experience.

Furthermore, ChatGPT serves as an invaluable educational resource. By offering curated information about nutrition, exercise and overall well-being, it enables patients and survivors to actively participate in their care plans. Empowering individuals with knowledge not only promotes healthier lifestyle choices but also engenders a sense of agency in their recovery.

While ChatGPT undoubtedly offers a plethora of benefits, it is essential to recognize that it is not a replacement for professional medical advice. Rather, it complements the efforts of medical professionals, serving as a supplementary tool to enhance patient-centered care.

In the realm of cancer care, where empathy, information and support are crucial, ChatGPT emerges as a compassionate and knowledgeable partner. As we embrace the digital age, harnessing AI technologies like ChatGPT can truly transform the cancer care landscape, fostering a community where patients and survivors are empowered, informed and uplifted throughout their journey.

CURE asked ChatGPT itself to write an article on the benefits of ChatGPT and artificial intelligence for patients with cancer and survivors.

ChatGPT Agrees: Tread Lightly When Asking AI About Cancer Care

"It occurred to me that modern technology, (such as) wearable devices, could be a nice tool to get a sense of what’s happening to our patients in a more complete sense,” said Dr. Nitin Ohri, a radiation oncologist, during an interview with 

. “Over the years, I’ve learned we do our best to evaluate our (patients with cancer), and they do their best to tell us how they’re feeling and what they’re experiencing.”

Ohri realized that communication between doctors and patients can sometimes be imperfect and that important information sometimes is lost in translation.

He noted that time and availability constraints could contribute to some of the loss in communication.

“We’re not with our patients 24 hours a day; we’re seeing them at snapshots in time, typically in the clinic, not in their native home settings,” he said. “We only get a very specific view of the patient’s experience.”

Ohri has been an associate professor and radiation oncologist for 11 years at Montefiore Medical Center and Albert Einstein College of Medicine in New York, with a primary concentration on lung and gastrointestinal cancers. He previously helped lead his team’s clinical trials and has focused on patient-generated health data, specifically with patient-reported outcomes and wearable monitoring device data, to further care for patients with cancer.

Wearable monitoring devices, such as Fitbits and Apple Watches, are typically used as fitness trackers but are becoming more advanced with the addition of health metric tracking. Now certain monitoring devices can track heart rate and irregular rhythm, blood oxygen levels, breathing rate, skin temperature and more. Some have even advanced to electrocardiogram tracking via the device and a smartphone app.

For patients with cancer, these wearable monitoring devices have the potential to aid doctors by collecting medical data. “The idea is that these devices are available, very-user friendly, relatively inexpensive and they’re becoming more and more powerful,” Ohri said.

The rising popularity of fitness trackers sparked an idea in his mind: What if patients used these devices to help inform doctors about how diseases and treatments affected their daily lives? Ohri carefully considered the logistics and how these devices could ultimately benefit both patients and doctors.

“There (are) so much data that could be collected relatively easily if we were to provide our patients with these devices. The activity data like step counts (are)
far more objective and will be far more meaningful than more subjective measures, such as the performance status that we assigned to patients, which is often misleading,” he said. “So the potential benefit to the patients would be that their doctors have a better understanding of how the patients are doing and the kind of aggressive treatments they are likely to tolerate or not tolerate, or perhaps proceed when there’s a risk for severe toxicity or hospitalization in the next few days.”

He acknowledged that utilizing wearable monitoring devices for patients was still not a common practice and that doctors are not yet used to reviewing the activity data collected from the devices. “At present, I believe it’s still something where we need to do a lot of clinical research to make this something that becomes more standard,” Ohri said.

Still, there are still several aspects of accessibility to be considered. “It’s imperative that (doctors) are the ones providing the devices,” he said. “We help collect the data or do all the data collection ourselves, so that all of our patients can have the opportunity to benefit from this monitoring.”


Ohri recommended that patients with a cancer diagnosis or who are receiving treatment who already have wearable monitoring devices should continue wearing them. “If you notice any changes, I think it’s worth mentioning to your doctors. They may or may not be used to thinking about things like step counts in their patients, but I think the extra information can only help.”

Using a device such as a Fitbit or Apple Watch can make a big difference for patients and doctors.

Wearable Monitoring Devices Can Help With Cancer Care Communication

When Shawn* received a diagnosis of a neuroendocrine tumor in September 2022, he never imagined that just a year later, he would also be told he has diabetes.

“My doctors believe the immunotherapy I was receiving may have induced the diabetes,” says Shawn. “I’m currently successfully managing my diabetes with the help of an insulin pump.”

Although rare, Shawn’s dual diagnoses have been documented in other patients who undergo immunotherapy, which rarely cause the immune system to turn on certain tissues — including the islet cells in the pancreas which produce insulin.

Results of research published in the journal 

 found that after treatment with checkpoint inhibitors, approximately 1% of patients developed a type of insulin-dependent diabetes.

Dr. Zoe Quandt, an endocrinologist at the University of California San Francisco (UCSF) Medical Center, cares for patients, including Shawn, who develop hormonal side effects from their cancer treatments.

She says both cancer and subse- quent treatments can cause metabolic changes that trigger or aggravate high blood sugar.

“Immunotherapies have proven to be effective cancer treatments that work by enabling the patient’s own immune system to fight cancer,” Quandt says. “Since immunotherapies stimulate a patient’s immune system and kill cancer cells, they can also cause elevated blood sugar levels and present a challenge for physicians to treat.”

In addition to checkpoint inhibitors, research has found that medications used to fight cancer, including corticosteroids and phosphoinositide 3-kinase (PI3K) inhibitors, can also cause diabetes. Some forms of chemotherapy, including 5-fluorouracil, asparaginase, busulfan and cisplatin, have also been linked to high blood sugar levels.

Dr. Matthew P. Wahl, an endocrinologist with University of Utah Health in Salt Lake City, says corticosteroid medications such as dexamethasone, often prescribed to combat nausea during cancer treatment, have been shown to raise blood sugar levels in some patients.

“If patients see a rise in blood sugar, we will work with them to adjust their insulin (dosing as needed),” Wahl says. “In some cases, drug-induced diabetes may be reversible after the medication is discontinued, while in other cases it’s a permanent condition.”

Although secondary diabetes can be a side effect of some of the therapies used to treat cancer, Wahl says other patients with cancer may have undiagnosed diabetes prior to beginning treatment.

One study, published in 2021, found that approximately half of patients with cancer reported new onset of type 2 diabetes after cancer diagnosis and treatment.

“We know there are shared risk factors for cancer and diabetes including advanced age, obesity and smoking,” says Dr. Kevin Schleich, a clinical pharmacy specialist at the University of Iowa Hospitals & Clinics in Iowa City. “Some (patients with cancer) may have an underlying case of diabetes that wasn’t previously diagnosed or high blood sugar levels that were elevated to diabetic levels after beginning cancer treatment.”

Schleich says doctors closely monitor each patient’s daily blood sugar and A1C levels when they’re undergoing cancer treatment to ensure blood sugar levels are well-controlled and that patients don’t develop ketoacidosis.

“While we don’t want to see high glucose levels in the long-term, they’re sometimes tolerable for a couple of days, when a patient with type 2 diabetes is undergoing cancer treatment,” Schleich says. “If they’re already on insulin, we may slowly increase their insulin dosages, where other previously insulin-naïve patients may need the addition of insulin on cancer therapy days.”

Quandt and Dr. Robert Rushakoff, clinical director of the UCSF Diabetes Clinic at Mount Zion, collaborated with the UCSF Infusion Center to develop a hyperglycemia management protocol for patients with cancer experiencing elevated blood sugar levels. The protocol is provided through an urgent care site within the infusion center, and Quandt says their model can be replicated at other infusion centers to offer a rapid response for patients who experience a rapid rise in glucose levels.

According to the protocol, Quandt says the urgent care team must decide if the patient with cancer experiencing hyperglycemia should be sent to the emergency department or if they can safely be treated at the infusion center.

“The protocol helps providers determine the amount of insulin and fluids to give the patient so they can safely continue with their cancer treatment that day,” Quandt says. The protocol also promotes patient education by encouraging staff to teach patients how to use a glucometer and insulin pen and to provide individualized nutrition counseling.

Diet and Lifestyle Changes Can Make a Difference 

With both diabetes and obesity on the rise, the World Health Organization recently noted that obesity may overtake smoking as the main risk for preventable cancer. High-quality diets have been shown to play a crucial role in preventing obesity, managing diabetes and lowering the risk of cancer.

According to the American Cancer Society and the American Diabetes Association, a diet containing fresh vegetables, whole grains, fruits, low-fat dairy or non-dairy products and lean meats can benefit patients who have been diagnosed with both cancer and diabetes. This type of diet can also reduce the risk of heart and kidney disease because diabetes, particularly type 2, increases the risk of developing these conditions.

“We always encourage patients to meet with a dietitian who can help them adopt a balanced meal plan,” Schleich says. “A dietitian can work with patients to devise an individual and consistent plan while also addressing issues such as what foods to eat in the event they feel nauseous or fatigued.”

Schleich notes that a patient’s blood sugar levels need to be well-managed during cancer treatments and that loss of appetite, a common side effect of cancer therapy, can lead to low blood sugar levels.

One recent study found that patients who had both advanced breast cancer and diabetes reported better long-term outcomes when their blood sugar levels were well- controlled, as opposed to those with uncontrolled blood sugar levels.

Quandt says this is where an individualized approach to helping patients with cancer control their diabetes comes into play.

“We like to see a patient’s A1C under 7% and we encourage them to give up habits such as smoking and alcohol that can make their prognosis worse,” she says. “Yet when a patient has done all of that and says sweets are the only thing left that gives them happiness, we’re going to determine how they can continue to enjoy ice cream without raising their blood sugar.”

One of the first things Quandt’s patient Shawn did shortly after receiving his cancer diagnosis was meet with a dietitian. He says the guidance he received was invaluable.

“My initial focus was on improving my diet and, as a result, managing my diabetes has been easier than I anticipated,” he says. “The dietitian

I consult with specializes in cancer care and believes my dietary focus will improve my long-term outcome.”

By learning how to best manage side effects of his cancer treatments and diabetes through diet, Shawn says he’s also been able to maintain an active lifestyle. 

“Whenever I have free time, you can find me on the tennis courts or on my mountain bike,” he says. “I can’t emphasize enough how important good nutrition is. I truly believe it’s the Holy Grail to successfully treating and keeping cancer at bay.”

Although researchers have established a clear link between diabetes and cancer, Quandt says there’s a need for continued research into why some cases of diabetes seem to be a side effect of cancer treatments and what can be done to reduce the risk.

“Some research shows the diabetes medication metformin is associated with a decreased risk for all cancers,” Quandt says. “With other agents, a lot of the research is inconclusive as to whether they can cause cancer or prevent it.”


Quandt notes some previous studies have also shown a link between long-term increased insulin levels raising the risk of certain types of cancer, including breast, prostate and colorectal.

Schleich says cancer treatments, as well as research on survival rates for cancer and diabetes, have improved since he was a resident in 2013.

“The field has seen significant improvements with immunotherapy and other treatments that have greatly improved cancer survival rates compared with what they were a decade ago,” he says.

LaCrecia Day of Birmingham, Alabama received a diagnosis of triple-negative breast cancer in October 2020 after discovering a lump.

“I went to a clinic that did 3D imaging, and they provided same-day results,” Day says. “The radiologist saw something on the imaging that was probably cancer and sent the images to a pathologist for a second opinion.”

From that moment, things moved fast. Day had a biopsy three days later and was referred to a surgeon, who thought the best course of action was to shrink the tumor through four weeks of chemotherapy before scheduling surgery.

“By the time I had my surgery, the tumor had doubled in size and was over 5 centimeters, and my diagnosis changed from stage 1 to stage 2 cancer,” Day says.

When a hematoma developed in her chest after surgery, her doctor discovered she had an A1C of 8% and subsequently diagnosed her with diabetes.

“I was initially prescribed metformin and later Jardiance (empagliflozin) and Ozempic (semaglutide), and my A1C is now below 7% and continuing to decrease,” she says.

Day also met with a nutritionist to determine foods that would keep her diabetes in check but also be palatable during her cancer treatments.

“I found eating fish and vegeta- bles satisfied my appetite and were easier to digest than meat and processed foods,” she says.

With her cancer now in remission, Day says her doctors believe her diabetes is also reversible.

“My advice to other patients affected by diabetes and cancer is to ensure all of your doctors are communicating so that you can get quality care,” Day says. “Cancer can be an isolating experience and it really helped me to connect with NowIncluded.com, a Black online health community platform, where I was able to share my story and read stories from other (patients with cancer).”

Schleich agrees, adding that patients with a diagnosis of both cancer and diabetes should never assume their other health providers know about the other services they’re receiving and medications they’re taking.

“Patients need to be proactive and ensure they communicate with their providers about any health changes that have occurred since their last appointment,” he says. “Take notes when you talk with your doctors and be sure to ask questions.”

Shawn says he has what he calls a “baseball team” of nine multidisciplinary providers on his diabetes/ cancer care team.

“The ninth slot is the designated hitter when I need to sub in a specialist,” he says. “I think it’s important to treat the whole body, and I have an oncologist, nuclear oncologist, immunotherapy oncologist, therapist, psychiatrist, nutritionist, acupuncturist and massage therapist on my winning team.”

* For the purposes of anonymity, Shawn will be referenced by first name only.

Patients "need to be proactive" as they coordinate care between two diseases.

First Cancer, Now Diabetes

In spring 2021, Kathy Ventre, 56, of Cincinnati, sensed something wasn’t right. She felt what she describes as menstrual cramps. She also felt tenderness near her ovary, as though she were ovulating. Yet, she was five years past menopause.

Ventre wondered why she felt like she was going to menstruate. “I even had acne all over my face,” she says. “It was strange.”

She saw a gynecologist. “He did an exam and didn’t feel anything,” Ventre says. “But he said, ‘You took the time to come in, so let’s do an ultrasound.’ ”

She underwent both an abdominal and a transvaginal ultrasound. She also had a blood test to check for CA-125, a protein sometimes elevated in people with ovarian cancer. Above 35 units per milliliter is considered high — Ventre’s level was 300. A CT scan confirmed a tennis ball-sized mass on her left ovary.

“Ovarian cancer symptoms are vague,” says Dr. Amy Bregar, a gynecologic oncologist and surgeon at Massachusetts General Hospital in Boston. “Things like bloating, weight gain, feeling full after eating — all of us experience those symptoms at one point or another.”

In May 2021, Ventre had a complete hysterectomy. The diagnosis was stage 3 high-grade epithelial ovarian cancer. Twenty days later, she began chemotherapy, with six rounds of carboplatin and Taxol (paclitaxel).

Surgery followed by chemotherapy is the first-line treatment for many patients with ovarian cancer. But ovarian cancer recurs in approximately 70% of patients, according to the Ovarian Cancer Research Alliance. Still, there’s reason for optimism with the potential of new developments in ovarian cancer treatments.

What’s transpired in ovarian cancer research in the past few years has been revolutionary, says Dr. Anil K. Sood, a gynecologic oncologist at The University of Texas MD Anderson Cancer Center in Houston.

“There are many biologically targeted drugs, such as (the tumor blood vessel formation inhibitor) drug Avastin (bevacizumab), PARP [Poly (ADP-ribose)] inhibitors and antibody-drug conjugates such as Elahere (mirvetuximab soravtansine). There are also immunotherapies that are being developed and tested,” he says. “We want people to understand they have a lot more options now for treatment than we did 15 years ago. And that portfolio of options continues to expand rapidly.”

Elahere made history in 2022 as the first antibody-drug conjugate approved by the Food and Drug Administration (FDA) for treatment of patients with platinum-resistant ovarian cancer, and the first approval since 2014 for this patient population.

PARP inhibitors — drugs that block enzymes that repair damaged cell DNA, preventing cancer cells from making repairs, leading to their destruction — were primarily used starting in 2014 to treat patients with recurrent BRCA-mutated ovarian cancer and as maintenance for those with newly diagnosed and recurrent platinum- sensitive disease.

In 2022, three PARP inhibitors that had been approved by the FDA were voluntarily removed by their companies for efficacy issues, specifically Lynparza (olaparib), Rubraca (rucaparib) and Zejula (niraparib), Dr. Ursula A. Matulonis, chief of the division of gynecologic oncology and the Brock Wilson Family Chair at Dana-Farber Cancer Institute in Boston, says. Matulonis was co-principal investigator of the SORAYA trial, the findings of which were the basis of the FDA’s approval of Elahere.

Ovarian cancer treatments were traditionally were based on observation, surgery and chemotherapy. But antibody-drug conjugates — which, as explained by the National Cancer Institute, target proteins found on cancer cells, then latch onto the cells and deliver cancer-fighting drugs — are a more targeted approach.

Elahere’s approval by the FDA, Matulonis says, “is definitely a step forward for our patients.”

Epithelial carcinoma is the most common type of ovarian cancer. Tumors grow in the tissue that lines the fallopian tube or covers the ovary (epithelium). Pathologists assign a grade — low or high — based on how the tumor looks under a microscope. Epithelial carcinoma may also be serous subtype (beginning in the serous membrane) or nonserous.

There are also rare types of ovarian cancer, including mucinous carcinoma and ovarian clear cell carcinoma.

“Ovarian cancer is not one disease,” says Sood. “Getting the right diagnosis and making sure the right subtype is diagnosed are critically important.”

Information about a patient’s specific genetic mutations and a tumor’s molecular makeup helps oncologists recommend personalized targeted therapies such as PARP inhibitors.

“I had genetic testing and learned I had a mutation in the BRCA1 gene,” says Ventre. “That made me a good candidate for a PARP inhibitor.”

PARP inhibitors show promise in treating women with BRCA gene mutations. They also help people who have homologous recombination deficiency, a defect in the specific pathway cells use to repair themselves.

“PARP inhibitors are an important part of treating patients with ovarian cancer,” Sood says. “We also know there are many patients who, despite receiving a PARP inhibitor, either don’t derive benefit from it or it works for a period of time and then their cancer starts to grow.”

Sood and his colleagues recently studied ovarian cancer cell lines that were either homologous recombination (HR) deficient or HR proficient. Their goal was to “see if there are drugs that could amplify or improve the effectiveness of PARP inhibitors,” Sood says.

 After testing cell lines with 335 different drugs, researchers found four drugs that combined well with Lynparza. They then evaluated clinical data on the toxicity of these drugs.

“Taking all that into account, we focused on a drug called CT-7439,
a specific inhibitor of cyclin- dependent kinase (CDK),” Sood says, noting initial validation studies indicate it combines well with Lynparza. “We’re excited about this.”

Pairing a PARP inhibitor with a CDK inhibitor could make PARP inhibitors more effective.

Sood hopes to test in animal models next to learn whether the combined drugs may provide more benefit than PARP inhibitors alone in some patients. He adds that researchers also hope to improve the effectiveness of PARP inhibitors and prevent adaptive resistance.

These findings are good news for women like Ventre, who experienced cancer recurrence after 18 months on Lynparza. A scan showed four small cancerous spots in her abdomen, so she’s now on a chemotherapy regimen of carboplatin and Gemzar (gemcitabine).

She says she’ll soon begin treatment with drug Avastin.

“My doctor is reluctant to do a PARP inhibitor again so fast because the cancer figured out a way to work around it,” she says.

The goal is to achieve stability and use Avastin as a maintenance therapy, according to Ventre, who is now a volunteer for the Ovarian Cancer Alliance of Greater Cincinnati and the Woman to Woman support and mentorship program from the Ovarian Cancer Research Alliance.

Improving surgery for ovarian cancer is another area of study. An abstract presented at the 2023 American Society of Clinical Oncology Annual Meeting found that in patients with ovarian clear cell carcinoma, surgical removal of lymph nodes (lymphadenectomy) was associated with improved disease-free survival. But more research is needed to determine whether lymphadenectomy is beneficial in some people.

Debulking surgery, in which surgeons remove as much of a tumor as they can, is the first step for most women with ovarian cancer.

“The standard of care remains open surgery,” Bregar says. “But there’s ongoing research investigating whether minimally invasive surgery can be used for ovarian cancer.”

Also being studied is when to perform surgery.

“For high-grade serous ovarian cancer, we know it probably doesn’t matter whether you have chemotherapy or surgery first,” she says. “But while it’s probably equivalent in terms of overall survival, there may be less risk and less toxicity to have chemotherapy first.”

Sood says operating first isn’t always effective — some patients have so much cancer that complete surgical removal isn’t possible.

“We’ve gone to more personalized approaches,” he says. “We do laparoscopic assessment upfront for those patients who are surgical candidates. Those who are most likely to benefit from surgery go to upfront surgery. Our complete resection rates are high in that group. Patients whose cancer is such that it cannot be removed upfront receive neoadjuvant chemotherapy and then have surgery after three to four cycles.”

Elle Simone Scott, 46, of Salem, Massachusetts, was diagnosed with stage 1C3 ovarian cancer in 2016. She had surgery to remove her right ovary and fallopian tube, followed by chemotherapy treatment.

When cancer recurred in 2020, it had spread into her bladder and bowel. She was treated with three rounds of Doxil (liposomal doxorubicin) and cisplatin before having a complete hysterectomy and resection of her bladder and bowel.

Surgery was followed by three more rounds of chemotherapy.

“After that, my doctor told me it was in my best interest to go on maintenance therapy,” Scott says. “He didn’t know if he could ever cure me, but he told me I could live with ovarian cancer chronically and still have a good quality of life.”

After surgery, Scott took Lynparza for a year. But she developed a “terrible face rash” and says the drug wasn’t effective. She then joined a clinical trial where participants received the immunotherapy drug Opdivo (nivolumab), Avastin and the PARP inhibitor Rubraca (rucaparib). She ended her participation after experiencing severe gastrointestinal side effects.

Scott, who has enrolled in a new clinical trial of the antibody-drug conjugate Enhertu and Lynparza in treating patients with HER2-expressing cancers, remains a proponent of participating in ovarian cancer research.

“If it weren’t for people who are willing to go through clinical trials, we wouldn’t have the groundbreaking medicine we have today,” she says, adding that if you’re in a clinical trial, it’s important to pay attention to your body. “When something doesn’t feel right, communicate with your medical team. Ask them to give you what you need to be successful.”

Research studies have led to deeper understanding of how best to treat patients with different ovarian cancer types. Bregar notes that chemotherapy doesn’t work as well in low-grade serous cancers (about 10% of ovarian cancers). 

“Low-grade cancer tends not to be as sensitive to chemotherapy when compared with high-grade cancers,” she says. “These cancers may be more hormonally driven. This is why we think hormone maintenance is so important.”

Bregar and her colleagues recently published a retrospective study on the benefit of oral hormone therapy for a subset of patients with low- grade ovarian cancer after treatment with surgery and chemotherapy. Patients in this subset who received surgery and chemotherapy followed by hormone maintenance had a 60-month survival rate of 71% compared with 61% among patients who did not initiate maintenance hormonal therapy — an increase in life expectancy of about 3.6 months.

Using results from a randomized controlled trial showing benefits of hormone maintenance, Bregar and her colleagues looked back at previously treated patients. “What we found confirmed that patients with low-grade serous cancers benefit from hormone maintenance,” she says.

“For low-grade ovarian cancers, we know hormones work in the maintenance setting.”

Bregar also notes that a lack of screening for ovarian cancer often leads to later diagnosis. “Ovarian cancer is rare,” she says. “Lifetime risk is only 1.4%. Because symptoms are so vague and there’s no way to screen, it’s like finding a needle in a haystack.”

She says more research is needed on how to detect ovarian cancer sooner.

“Something I’m looking at is whether we can find a way to diagnose ovarian cancer early by doing what we call a uterine lavage, or washing of the uterus,” she says.

What Role Do Integrative Therapies Play? 

It also is critical to treat the whole person, not just their cancer. 

“We know the psychological aspects or stress aspects of cancer are so important,” Sood says. Whole-person care is a critical focus for Dr. Tara Berman, a medical oncologist specializing in gynecology at the Inova Schar Cancer Institute in Fairfax, Virginia, and an expert in integrative oncology services. Earlier this year, Berman and her colleagues published a review of clinical research supporting the effectiveness of integrative modalities in ovarian cancer care.

According to Berman, these services include three components: mind and body practices, natural products and lifestyle modification.

“They’re not meant to supplant conventional cancer treatments,” she says. “Integrative oncology is about using other modalities in conjunction with standard of care to help improve quality of life and ideally, efficacy outcomes.”

Integrative oncology services, which include nutrition, exercise, massage, acupuncture and emotional support, help improve quality of life, she says. They also help patients tolerate and better adhere to treatment, Berman notes.

They can also help manage side effects. “Massage increases circulation and blood flow,” she says. “And acupuncture is helpful in the setting of chemotherapy-induced neuropathy.”

Berman says data are beginning to “scratch the surface” of integrative oncology’s potential — for example, the role of fat cells in certain cancers.

“Estrogen can be a driver for promoting the growth of cancer cells,” she says. “In some ovarian cancers, tumors have estrogen receptors. Even though we block estrogen by taking out the ovaries and giving certain hormonal medications, estrogen is also produced by fat cells. So, through diet and exercise, by reducing body mass index and the amount of fat in the body, we can effectively reduce estrogen levels.”

Recent developments in PARP inhibitor combinations and antibody-drug-conjugates are changing the landscape of ovarian cancer treatment. 

Optimism Abounds in Ovarian Cancer Research

Software engineer Katie Coleman has incorporated technology into every stage of her journey with kidney cancer since receiving her diagnosis two and a half years ago.

“I was diagnosed at 29, and I didn’t know really anything about cancer at the time,” says Coleman, who lives near Austin, Texas. “But as I found myself navigating through the system as a patient, I was shocked at how little technology seemed to be integrated in the whole process and system. When you come down to treatments and some of the tools that are actually used in the medical space, tech has come a long way there, but it didn’t seem like tech has come a long way to really help patients.”

Coleman received a diagnosis of stage 4 kidney cancer — oncocytoma, which, as explained by the National Cancer Institute’s Center for Cancer Research in a 2022 article about Coleman, comprises 15% to 20% of kidney tumors and is typically benign. What made Coleman’s case rare, the National Cancer Institute noted, is that her tumor had spread, making hers “likely the only known case in the United States and one of only a handful throughout the world.”

“Because I have such a rare cancer, I was seen by lots of different physicians at lots of different institutions, and I got to experience how frustrating that is when your data doesn’t sync up and you’re sending things by fax that get there half of the time (or) you’re mailing things. It’s a very slow, tedious process,” Coleman tells 

Coleman created an app that allows patients to streamline their doctors’ information. In addition, she utilized online support groups and developed a following via TikTok, X (formerly Twitter), Instagram and YouTube and her “Oncology Unscripted” podcast.

Now a software engineer for the Rare Cancer Research Foundation, Coleman recently experimented with using the latest iteration of AI chatbot ChatGPT to create a spreadsheet and track her medical expenses in anticipation of filing
her taxes next year. It was a task that would have taken hours, or a day, for her to complete on her own — and, she says, ChatGPT got it done “in about a minute.”

“I was trying to figure out if I would be able to reach the limit for my medical expenses by adding them all up, if it would be higher than the standard (tax) deduction,” Coleman says. “And so I consolidated all my medical expenses, and then kind of put that (into ChatGPT) and had it generate a table for me and sum them up, which I could have done on my own but it would have taken a really long time.”

Artificial intelligence platforms, including ChatGPT, offer many benefits, but some experts remain skeptical of the technology’s trustworthiness.

CURE Fall 2023