Centering discussion on a patient scenario of stage II HR+ breast cancer, expert panelists consider how they would approach workup and selection of therapy.
Jules Cohen, MD: Welcome to this CancerNetwork® presentation titled “Optimizing Treatment for HR+/HER2- Metastatic Breast Cancer.” I’m your host, Dr Jules Cohen. I’m an associate professor of clinical medicine at Stony Brook University in Stony Brook, New York. Some colleagues are joining me today. I’m going to invite them to introduce themselves. We’ll start with Dr Mortimer.
Joanne Mortimer, MD, FACP, FASCO: I’m Joanne Mortimer, the director of the women’s cancers program at City of Hope in Duarte, California.
Jules Cohen, MD: Dr Slamon?
Dennis J. Slamon, MD, PhD: I’m Dennis Slamon. I’m a professor of medicine at UCLA [University of California, Los Angeles] David Geffen School of Medicine [in Los Angeles, California].
Jules Cohen, MD: Dr lyengar?
Neil M. Iyengar, MD: I’m Neil Iyengar, an associate attending at Memorial Sloan Kettering Cancer Center and an associate professor of medicine at Weill Cornell Medicine in New York, New York.
Jules Cohen, MD: Thank you. We’re going to review data presented at recent conferences and discuss challenges or strategies for the treatment of patients with HR [hormone receptor]–positive metastatic breast cancer. Let’s begin.
I’m going to read a clinical scenario, and then we can discuss. A 60-year-old woman, who was diagnosed with cancer 5 years ago, is being seen at your practice. She has 3 children and no family history of cancer, and she underwent menopause at age 50. Her past medical history includes obesity, and hypertension that is controlled with medication. She is a former smoker, about a pack per day for 10 years. In terms of her family history, her mother had breast cancer in her late 70s, and her father, also a smoker, died of lung cancer.
On exam, she has a palpable lump in the left breast in the upper outer quadrant. Imaging showed a 1.5-cm mass in the upper outer quadrant of the left breast, as well as a 1.1-cm left axillary lymph node. Biopsy of the breast lesion showed ER [estrogen receptor]–positive, PR [progesterone receptor]–negative, HER2 [human epidermal growth factor receptor 2]–negative invasive ductile carcinoma. There was no evidence of distant metastases on imaging. She underwent a left lumpectomy and sentinel lymph node biopsy and pathology, which showed a unifocal invasive ductile carcinoma that was 1.7 cm, and 1 of 2 sentinel lymph nodes was positive for metastatic carcinoma. She was staged as a stage II T1CN1M0, and she was treated with aggressive adjuvant therapy: including dose-dense doxorubicin cyclophosphamide and paclitaxel, followed by radiation therapy and then anastrozole for a 5- to 10-year course.
Dr Mortimer, would you have done anything different regarding the patient’s initial testing or imaging?
Joanne Mortimer, MD, FACP, FASCO: This woman would have been a candidate for the RxPONDER trial and probably should have had her primary tumor submitted for oncotype testing. Then the determination of chemotherapy would have been on the basis of her oncotype testing. If her oncotype testing was low, then we probably wouldn’t give her chemotherapy.
Jules Cohen, MD: Do you want to talk about the RxPONDER trial and how it differs for pre- and postmenopausal women?
Joanne Mortimer, MD, FACP, FASCO: RxPONDER took pre- and postmenopausal women with lymph node–positive disease—1 to 4 positive lymph nodes. They looked at the oncotype score, randomizing patients to receive chemotherapy with endocrine therapy for individuals with a lower oncotype score. Everyone with oncotype scores of 25 or more got chemotherapy. The lower group of patients were randomized to receive endocrine therapy with or without chemotherapy. In the premenopausal group, there appears to be an improvement from progression-free survival for individuals who received chemotherapy. However, in postmenopausal women, there isn’t a need to give chemotherapy. If this patient had had a lower oncotype score, she wouldn’t have been recommended for chemotherapy. But if her oncotype score was high, she would have gotten chemotherapy.
Jules Cohen, MD: Dr Iyengar, I have a question. Premenopausal women with node-positive disease always get chemotherapy. We don’t know if it’s the chemotherapy that prevents or reduces the risk of metastatic recurrence or if it’s the premature ovarian failure that the chemotherapy produces. One question I have for the postmenopausal women is if their Oncotype DX score was 26 or above, would you give them hydrochloride, cyclophosphamide, paclitaxel? Or would you stratify their chemotherapy based on whether their oncotype score was 25 to 31 or over 31?
Neil M. Iyengar, MD: That’s a great question. I’ll first address your comments on the premenopausal population because that’s an important consideration. We saw updated data from Dr Antonio Sparano at the San Antonio Breast Cancer Symposium this year. The premenopausal group, with a higher-range score of 21 to 25, appeared to benefit from chemotherapy in the adjuvant setting. Premenopausal women with slightly lower scores starting at 16 appeared to have some benefit if they were also clinically high risk. Even in that population, we’re still using clinical features to help stratify who may benefit from chemotherapy.
In the postmenopausal population, as Dr Mortimer pointed out, the benefit of chemotherapy wasn’t observed for scores less than 25. To address your question, which is very relevant, the oncotype score hasn’t been validated for the selection of a chemotherapy regimen. I wouldn’t use it necessarily as a selection tool for the chemotherapy regimen, but as a binary yes or no: should I be using chemotherapy in this patient? We can look to clinical features. We can also look at the RSClin tool, which incorporates the oncotype, to give us a better perspective on that particular patient’s risk and whether we should be using anthracycline-based therapy or an anthracycline-sparing regimen.
Jules Cohen, MD: Dr Slamon, can you clarify the difference between the TAILORx trial and the RxPONDER trial? How do they inform our decision on whether to give chemotherapy?
Dennis J. Slamon, MD, PhD: This is parsing it in a very small amount. The differences are very small. It’s useful. We don’t use that as much as clinical features. Oncologists like a number to decide, but you need good pathology. In the comparison done in The Royal Marsden, looking at clinical features done by central pathology vs oncotype, when you look at all the 4 things—ER, PR, HER2, and proliferation status—it didn’t add much. It adds more than $3000 at the cost of taking care of the patient. Except in those really marginal cases, I don’t think it’s called for, so we don’t use it as much.
Jules Cohen, MD: You feel that you can make these decisions without the help of the oncotype. You feel you can rely on the conventional clinical and pathological data. That’s good. Dr Mortimer, how similar is this patient to those in your practice? Is there anything different or notable about this patient, or about your patients with HR+ disease in general?
Joanne Mortimer, MD, FACP, FASCO: RxPONDER has made us change how much neoadjuvant therapy we use. This woman had a palpable nodal presentation. Many times, people assume that if you have a positive node, then you should give chemotherapy because this is aggressive disease. RxPONDER taught us that if you identify somebody, if you go to surgery first in hormone-positive breast cancer, complete responses are rare. Down-staging them for lumpectomy may be a reasonable expectation of neoadjuvant therapy, but pathologic complete responses are not. RxPONDER taught us that we should probably take these women to surgery and find out their biology before we make a decision on how to treat them systemically.
Transcript edited for clarity.