In this recording of Oncology Data Advisor's Live Breast Cancer Panel, three noted experts partake in a conversation about recent advances in treatment, strategies and integrative medicine modalities to minimize toxicity, and techniques for delivering patient-centered care.
Oncology Data Advisor: Hi, everyone. Welcome to Oncology Data Advisor. I'm Keira Smith. Thank you so much for joining us. Today we're having a panel discussion in honor of Breast Cancer Awareness Month. Today I'm here with Christine Samuel, who is an advanced practice provider at MD Anderson Cancer Center; Mikel Ross, who is a nurse practitioner at Memorial Sloan Kettering Cancer Center; and Lillie Shockney, who is a Professor of Surgery at Johns Hopkins University. Thank you all for joining us. We're excited to have a great discussion today.
To start us off, Christine, what are some of the current treatments for patients with metastatic triple-negative breast cancer, or TNBC?
Christine Samuel, MSN, APRN, AGPCNP-C: As you know, because triple-negative breast cancer doesn't have the estrogen, progesterone, and human epidermal growth factor 2 (HER2) receptors on the surface, unfortunately, there are not a lot of therapies. Chemotherapy is still one of the mainstays, but in the past couple of years, we've had some new drugs, such as poly–adenosine diphosphate polymerase (PARP) inhibitors for patients who are BRCA1- or BRCA2-positive, and also for triple-negative breast cancer. Immune checkpoint inhibitors like atezolizumab and pembrolizumab have also been approved within the past two or three years to help with advanced disease, usually as a third line. There was also a new antibody-drug conjugate that was recently approved, sacituzumab govitecan. We're getting more targeted therapies, but unlike with hormone-positive breast cancers, there's still a lot of research that needs to continue to find effective treatments for the triple-negative population.
Oncology Data Advisor: What are some of the other recent advances that have been done in metastatic TNBC research?
Christine Samuel: The new PARP inhibitors have been approved within the past few years; in 2020, olaparib was approved for BRCA-mutated HER2-negative metastatic breast cancer. Talazoparib—I actually worked on that study—was also approved by the FDA in October 2018 for BRCA-mutated HER2-negative disease. Those are both oral drugs that are tolerated fairly well. There's also atezolizumab with a taxane, which is paclitaxel. I also participated on that study. Even though the overall objective response rate is around 15% to 20%, the results are better for patients who are programmed cell death protein 1 (PD-1)–positive. There's also been new research in the metastatic setting with anti-TROP2 drugs in the third line, and that's the new antibody-drug conjugate, sacituzumab govitecan.
Oncology Data Advisor: What are some of the ways that you anticipate that treatment will continue to evolve in the coming years?
Christine Samuel: I think they're going to continue to do more research and try different combinations with a variety of clinical trials, in order to find new pathways to fight this disease. The prognosis is very poor, and we need to try to find a way to get the immune checkpoint inhibitors to become more efficacious.
Oncology Data Advisor: Thank you so much for giving us that really comprehensive overview.
Christine Samuel: Thank you.
Oncology Data Advisor: Along with these newer treatments, Mikel, can you tell us about some of the more common side effects and the best strategies to manage them?
Mikel Ross, MSN, RN, AGPCNP-BC, OCN®, CBCN®: Absolutely, and thank you for that great overview, Christine. As we get new agents, what I find particularly interesting is we can continue to have some of the old nemeses in terms of side effects that continue to crop up, and we can think about treating the same old side effects that come up with these new agents with strategies that worked for older drugs. An example is the TROP2-directed antibody-drug conjugate that Christine talked about, sacituzumab govitecan. It's interesting in that, basically, it's a way to take an old-style drug, a topoisomerase inhibitor such as irinotecan, but in this case taking it with an antibody-drug conjugate and letting it be more selective. We run into exactly the same types of side effects that we see with irinotecan, which we have not used that much because of the side effect profile.
With sacituzumab govitecan, which has shown overall survival in the third-line setting, we still come across diarrhea, rash, and nausea. I think one has to be really creative at mixing and matching old strategies to manage these side effects with the newer agents and to not forget what we've learned in the last 30 years. Knowing that it's similar to irinotecan, I actually use atropine as one of the medications, right in the infusion chair. We always did it with irinotecan, and now I do it with sacituzumab govitecan, knowing that it will help control diarrhea. Then if that doesn't do the job with controlling diarrhea, then I reach for something called colestipol. Another trial called the CONTROL trial looked at minimizing discontinuation rates from a tyrosine kinase inhibitor called neratinib. We actually saw dramatic drops in discontinuation rates when we used something like colestipol as opposed to loperamide and atropine. We see some of the same side effects, but we can pull from the past on how to manage them, and those rules still apply.
Oncology Data Advisor: What are some of the more challenging side effects that come with hormone-sensitive or HER2-sensitive disease?
Mikel Ross: With HER2-positive disease, we use drugs like pertuzumab and the new triplet of tucatinib with trastuzumab and capecitabine from the HER2CLIMB study, which has also been great. Once again, there's the same old nemesis of diarrhea. One side effect that we've had to get a little bit smarter on with some of the new HER2-directed therapies such as trastuzumab deruxtecan is interstitial lung disease. This is a rare, uncommon side effect, but it's an adverse event of special interest, and this can be a side effect that can creep up on you pretty quickly. We've had to get a little bit better at recognizing this and being cognizant and moving very quickly. We've always moved quickly with things like paclitaxel-induced pneumonitis, but this is kind of a next-level respiratory side effect that we have to really be aware of and manage.
Then finally, in hormone receptor–positive disease, whether it's early-stage or even patients with metastatic disease, I find the management of estrogen deprivation side effects to be incredibly challenging, especially in the younger populations. We will take, in some cases, very young ladies in their thirties or early forties, and shut their ovaries down, taking them from a 30-year-old estrogen state to a postmenopausal estrogen state. It can be really, really challenging with the achiness and the hot flashes that come along with that. That I find heartbreaking, because it's genuine and it's hard. Because of the population you're dealing with, it can be a challenge.
Oncology Data Advisor: In addition to all these strategies, how do you fit integrative medicine modalities into your practice, and what side effects do they demonstrate benefit in addressing?
Mikel Ross: The side effects of estrogen deprivation—most commonly, hot flashes, achiness, and arthralgias/myalgias—tend to really be kind of tough for some people. That's one of the places where I utilize integrative medicine and our Integrative Medicine Service. There have been actual studies showing that acupuncture can help with, for example, aromatase inhibitor–associated muscular system symptoms and also with hot flashes. There was a paper in the Journal of Clinical Oncology in 2016 that showed that acupuncture plus self-care decreased hot flashes more than just self-care alone.
In terms of achiness caused by estrogen deprivation, there was a JAMA article in 2018 that showed that after 12 weeks of real acupuncture compared with sham acupuncture, there was a statistically significant decrease in terms of the pain scores in the two populations. If you got acupuncture, you did a lot better. I also find integrative medicine to be a great colleague and friend in terms of the management of insomnia. It's been demonstrated that cognitive behavior therapy, sleep hygiene, feedback, and meditation actually work better than pharmacology. I am so grateful that most of the comprehensive cancer centers have really embraced integrative medicine. It has so much to add, and reaching for the prescription pad is not always the right answer.
Oncology Data Advisor: Thank you so much for explaining all these great strategies.
Mikel Ross: My pleasure.
Oncology Data Advisor: To delve a little bit deeper into improving patients' quality of life, Lillie, how do you explain to a patient with metastatic TNBC what the goals of treatment are?
Lillie Shockney, RN, BS, MAS, HON-ONN-CG: Since the majority of breast cancer patients will have had an earlier-stage diagnosis—that could be a year ago, two years ago, five, even 10 years ago—at that time, our goal was to have them be cancer-free, a curative intent. Now that they've been diagnosed with metastatic disease—or for some patients, they may have been diagnosed from the beginning with stage IV breast cancer—we need them to understand that we're not looking at curing the disease. We're looking at controlling the disease and doing what we can to get the disease under control and have her live in harmony with this disease, very much focusing on quality of life. Quantity of life should not be the goal; quality of life should be. If you're just existing and you're miserable, that really is not a good idea for the patient or for their family.
Whenever I'm looking at research studies, they'll have graphs and charts showing that this patient survived three and a half months longer than these other patients in this other line of therapy. I'm the one that always sticks my hand up in the air and says, "How were they living? Were they living, or were they existing?" That usually causes the speaker to stop talking, because they may not know. I want to make sure that the patient is not receiving treatment for treatment's sake, but that there are goals of care and that those goals of care are driven by what the patient sees to be her goals.
Oncology Data Advisor: Can you explain what patient-centered care is and what milestones and life goals are?
Lillie Shockney: Patient-centered care has become a buzzword in the last, I'll say, five years. You may even see or listen to commercials on the radio saying, "We deliver patient-centered care." I haven't found very many facilities, though, that treat cancer patients that are truly delivering patient-centered care. What I mean by that is that the patient is more than her pathology and more than her staging workup. She had a life before she was diagnosed; we want her to have a life during her treatment, as well. She should not just be considered a stage IV triple-negative breast cancer patient. She's 38 years old; she's a fifth-grade school teacher and loves teaching; she got a divorce last year, which was her idea; she has a nine-year-old son who has autism; she loves bird watching; she enjoys going to chick flicks with her girlfriend. I want to know all of that about her so that we are able to really focus on her and her needs and see her beyond just her diagnoses.
One of the things that I ask patients—and this applies to all patients, not just those with stage IV disease—is to tell me any milestones that are coming up in the coming months. A milestone might be that her daughter's getting married, or she has her 10th wedding anniversary, or she's going to do a surprise party for her mother who's turning 75. I want to figure out how we can dovetail the treatment with those milestones so that we preserve those milestones rather than sacrificing them to the cancer. I'll tell patients, "I only want you to give this disease what it needs to get it under control. I don't want to steal away your social time, personal time, family time, not even your work time. If you love your job, or if you need to continue to work for financial reasons, I only want cancer to get what it needs to control it. Do not let it take over. You do not let it be in charge of your life."
Now for life goals, if it's a patient with an earlier stage, I'm going to say, "Where do you see yourself in one year, five years, 10 years?" I'll give you an example. I had a 29-year-old young woman diagnosed with stage IIB breast cancer. When I talked to her about her milestones and her life goals, I said "Where do you see yourself?" She said, "Well, I'm getting married in about a year." I said, "That's important for us to know." I have her tell me the date so we can work around what we're going to be doing for her treatment, because I want her to feel good on the day she gets married. You don't want a surgical drain sticking out underneath her wedding gown, for heaven's sakes. That would be terrible, or if she's nauseated from the chemotherapy that we gave two days ago. We need to preserve those milestones.
I asked her, "Do you anticipate having a family in the future?" She said, "Yes, we want to start a family about a year after we're married." I told her, "I'm going to get you into fertility preservation, because we're going be doing chemotherapy first, to shrink this tumor and shrink the lymph nodes that we also know are positive for breast cancer. If I don't get you into fertility preservation, you probably will sacrifice being a biological mom." Again, see, I don't want her to have this cancer be in control. I also asked her, "Tell me about her career path. I see that you are a bank teller at a local bank in downtown Baltimore. Do you see yourself as the president of the bank in 10 years?" She said, "Oh no, I work there because I really like the hours that I work. It's what I do in the evenings and on the weekends that I'm passionate about. I hope that will be my eventual career."
I said, "Tell me about that." She said, "I'm studying to be a concert pianist." I knew we were going to give her a taxane that was going to probably cause her peripheral neuropathy and tingling and pain in her fingers and toes. The possibility of her really becoming an excellent concert pianist was going to dwindle. I intervened and talked to the medical oncologist and said, "Hey, we need to look at a different protocol or a different chemotherapy regimen, or this woman may sacrifice what she's passionate about, what her career goals are, and where she sees her life goals in the future." He went, "Oh my heavens, yes." I told her, "We're going to give you treatments that may take a little longer before we do your surgery and then follow that with radiation, but you still should be able to become a concert pianist." If she's good at playing the piano, I didn't want her to be a patient who would say five years from now, when we finished her treatment, "Breast cancer's the worst thing that ever happened to me. I wasn't able to be a biological mom. I had to forfeit my career, and it's because of breast cancer." I would've said, "No, it's because your treatment team didn't deliver patient-centered care." For patients with stage IV disease, I want to know those milestones. Those are even more precious than ever for us to be able to preserve them. That might mean that we give her a drug holiday so that she's feeling pretty well for that 10th wedding anniversary.
For example, if her daughter's getting married, we definitely want to go to great lengths to make sure that for the window of time a few days before, and certainly the day of and the day after, she's feeling as good as we can have her feel. That will mean stopping treatment and giving her a break so that we can get these toxic drugs out of her system, so she's feeling as good as she can feel. When we look at life goals, her life goals might be, "I want to see my daughter married one day. My daughter right now is 10." I might be thinking, "You've got triple-negative disease. I'm not sure that's a realistic goal for you to physically be here to achieve that life goal." For many years, I would say, "I'm so sorry that you probably won't be here," when I know how important this is to patients. So about 25 years ago, I decided to develop some alternative ways for patients with metastatic breast cancer to fulfill their life goals.
In the case, for example, of someone who will not be here when their young children are adults, we provide cards for them to select. I get cards donated—very nice cards, high-end, $8 or $10 apiece—for the milestones that their children will achieve when they have their first confirmation or bar mitzvah, when they get their driver's license, when they graduate from high school and go to college, when they graduate from there, when they get the first career job, when they get married, when they have a baby. What do you want to tell your child on that day? They write in these cards, and then I ask them to put them in the hands of a family member who will be the keeper of the cards. I do recommend that these cards be kept in a safety deposit box at a bank, because they cannot be replaced. If there's a flood or fire, they're gone, and we can't replicate them, because she's gone. I've done this for about 25 years, and it works, because I am privileged to hear from children who are now grown adults. Oftentimes I've never met these kids.
I had one woman who contacted me, who said, "I never met you, but you took care of my mother 14 years ago when I was just 10 years old. My mother was in and out of the hospital a lot during the last year of her life. When my dad would bring her home, he would always recruit my Aunt Sarah, my mother's sister, to help take care of her. I would overhear my mother saying to Aunt Sarah, 'Lillie said to do this, and Lillie said to do that,' but I didn't know who you were or what you were telling my mom until my mother did pass away. My Aunt Sarah became the keeper of my cards. For every milestone in my life, there has been a card from my mother. I really have felt my mother's presence, and I respect her motherly advice and her love for me and her value system. I wanted to track you down, so I called Johns Hopkins and asked to be transferred to the breast center and asked if there is still somebody named Lillie there, and I got you on the phone."
"I wanted to tell you, three weeks ago, I got married. My Aunt Sarah, while she was helping me put on my veil, handed me a card from my mother. The edging of the envelope had yellowed, because the card was 14 years old. I opened up the envelope. It was a beautiful wedding card from my mom. As I looked inside, it was down the left-hand side that my mother had written with her blue pen. At the top she wrote, 'I know you would've chosen wisely who was deserving to have you spend the rest of your life with.' In the middle, she had marital advice: 'never go to bed angry with one another; whatever it is can be talked through.' At the bottom, she wrote, 'when your dad lifts your veil and kisses your left cheek, you will feel me kiss your right.' Miss Lillie, I swear to you, I felt my mother's kiss. I have always felt my mother's presence through these cards. I'm curious to know, is that my last card?" I said, "Do you anticipate having a family?" She said, "Yes, we want to start a family in about a year and a half." I said, "When you learn you're pregnant, there's a letter from your mother that describes how she felt when she knew she was carrying you. When the baby is born, there is a letter from your mother describing the first time she held you at the time of your birth and all of her hopes and dreams for you. Then when that baby is a toddler, your mother has recorded her voice saying nursery rhymes and children's stories. Your mother will be a grandmother actively involved in your children's lives."
This works, and I'm so thankful I don't have to say anymore, "I'm so sorry you won't be here." This has proven to be an effective way. It is something that I find metastatic breast cancer patients truly do embrace. I also had a patient who was going to become a grandmother, and she was very ill, triple-negative, and we were looking at just one to two months survival at that point. I spoke to her daughter, who was pregnant. I said, "How do you feel about your mom coming with you to meet the baby in ultrasound when you hit five months? That would really be a wonderful thing that you could do for her, if that's okay with you." She said, "That would be fabulous." This patient got to meet her grandson, her first grandchild, in ultrasound, and see that his little profile matched the daughter's profile, with the same nose. She took her hand and put it in the gooey jelly on her daughter's abdomen and said, "Look at this, I'm even holding the baby right now." We just have to be creative, rather than saying, "I'm so sorry."
Oncology Data Advisor: Thank you so much for sharing such a powerful story with us, and thank you so much, Lillie and Christine and Mikel, for sharing all this great advice. We really learned a lot today, so thank you again.
About Christine Samuel, Mikel Ross, and Lillie Shockney
Christine Samuel, MSN, APRN, AGPCNP-C, is a Lymphoma Research Advanced Practice Provider and a Senior Research Nurse at MD Anderson Cancer Center in Houston, Texas. She specializes in the treatment and management of patients with breast cancer.
Mikel Ross, MSN, RN, AGPCNP-BC, OCN®, CBCN®, is a nurse practitioner at Memorial Sloan Kettering Cancer Center, where he specializes in the treatment of patients with breast cancer. He is also the lead clinician for MSKCC's scalp cooling program, which seeks to minimize chemotherapy-induced hair loss. Mr. Ross has authored or coauthored numerous publications focused on oral therapy adherence and symptom management to optimize outcomes in patients with breast cancer.
Lillie Shockney, RN, BS, MAS, HON-ONN-CG, is the University Distinguished Service Professor of Breast Cancer and Professor of Surgery at Johns Hopkins Medicine. She is also Co-Founder and Director of the Academy of Oncology Nurse and Patient Navigators. Ms. Shockney specializes in the treatment and care of patients with breast cancer. She has written 20 books and published more than 300 articles on the topic of breast cancer management and survivorship.
Transcript edited for clarity. Any views expressed above are the speakers' own and do not necessarily reflect those of Oncology Data Advisor.