Considerations When Treating Premenopausal Patients With Breast Cancer

Genomic Testing, Chemotherapy, Adjuvant Androgen Therapy, and Survivorship Issues

At the 2022 Great Debates & Updates in Women’s Oncology virtual meeting, Matteo Lambertini, MD, PhD, University of Geneva San Bernardino Hospital, Geneva, Italy, presented the case of a premenopausal woman with hormone receptor positive, HER2-negative breast cancer.

In his presentation, Dr Lambertini discussed the different considerations clinicians should keep in mind when caring for younger patients with breast cancer — genomic testing, whether to use chemotherapy, which type of adjuvant endocrine therapy to administer, and issues of survivorship such as fertility and toxicity.

Transcript

Dear colleagues, my name is Matteo Lambertini. I'm a medical oncologist and professor of medical oncology at the University of Geneva, San Bernardino Hospital in Geneva, Italy. I'm particularly interested in the field of breast cancer in young patients. At the Great Debates and Updates in Women's Oncology meeting, I discussed a challenging clinical case of a premenopausal woman with hormone receptor-positive, HER2-negative breast cancer, a T2 of 2.5 centimeters, N1 for 1 positive node out of 12 removed, with a grade 2 disease, and a recurrent score of 19. While discussing this clinical case, we touches on 3 major challenges.

The first is the role of genomic testing in premenopausal patients. The second is the choice of whether to use chemotherapy in this specific scenario. The third important issue is which type of adjuvant endocrine therapy is to be given to this young patient. Finally, there are also survivorship issues like fertility, pregnancy, and toxicity of adjuvant endocrine therapy.

Regarding the first point, the use of genomic test in young patients, the main message is that genomic tests are also prognostic, among young patients. It's true that luminal-like cases in young patients have a higher incidence of high genomic risk, when tested with a genomic test. However, the prognostic value of this test is the same, as is possible in other patients, meaning that a low genomic risk in a young patient is still a low genomic risk.

In this specific case, we have the issue of a premenopausal woman with 1 positive node, and the recurrence score of 19, so it's in a gray area, whether to give chemotherapy or not, based on the data of the respondent trial, showing a survival advantage with the use of chemotherapy in these specific patients.

However, currently, adjuvant endocrine therapy is not the optimal treatment. Only a minority of the patients in the respondent trial received ovarian suppression as part of adjuvant endocrine therapy. Whether to give chemotherapy to this patient remains a difficult choice. I would tend to give chemotherapy, probably, in this specific case. Then, of course, there is the debate of using a TC regimen [docetaxel + cyclophosphamide] times six, or an anthracycline taxane-based chemotherapy regimen.

The second important point is use of adjuvant endocrine therapy. For sure, this is the most important treatment to be given to this patient. She has a T2N1 luminal-like disease. This is a patient that I would define as intermediate risk of recurrence, based on clinical pathological characteristics. I would use ovarian function suppression (OFS) as a part of adjuvant endocrine therapy, in this patient.

Then the decision between giving tamoxifen or an AI [aromatase inhibitor], together with the OFS, is based on several consideration. The first depends on whether I chose to give chemotherapy or not. With intermediary risk of recurrence, if I give chemotherapy, it will probably not matter too much, whether I give tamoxifen and an aromatase inhibitor. Of course, the higher risk of recurrence, the more I would be prone to give an AI together with OFS. However, here I think we have this intermediate risk.

If I decide not to give chemotherapy, I will give the most effective adjuvant endocrine therapy, which is the combination of OFS plus an AI. If we give an AI, in a premenopausal patient, we always must give it with OFS, and we must check regularly if the patient has a complete ovarian suppression, because we know that up to 20% of patients, treated with a pharmacological OFS plus an AI, are not completely suppressed. Obese patients, patients not receiving chemotherapy, patients that are very young, are at higher risk of not being properly suppressed with OFS. We need to pay more attention when checking the ovarian function of this patient during their follow-up.

The final important point, and a crucial aspect in the care of premenopausal patients, is discussing survivorship issues, including fertility and pregnancy-related concerns. If this patient is a candidate to receive chemotherapy, she's younger than 40 years of age, so she's a candidate to receive fertility preservation strategies. Meaning she will be counseled that chemotherapy may induce premature ovarian insufficiency, may induce infertility. If she's interested to increase her chances of having a future pregnancy, oocyte cryopreservation should be discussed before initiating chemotherapy. Following this strategy, or if the patient is not interesting in preserving fertility, but also does not want to have an early menopause, the use of ovarian suppression during chemotherapy should be discussed in these cases.

In addition, for challenging patients with luminal-like disease who receive adjuvant endocrine therapy, we need to prolong adjuvant endocrine therapy for 5 to 10 years. Meaning that, during this time window, they cannot have a pregnancy. Endocrine therapy, especially tamoxifen, is teratogenic. The safety data we have right now for pregnancy after breast cancer, in these specific patients, are for those that completed standard adjuvant endocrine therapies with around 5 years of treatment.

Soon, hopefully, at the San Antonio Breast Cancer Symposium, we will present the results of the positive trial that has investigated the safety of stopping adjuvant endocrine therapy before the standard duration of 5 years, between 18 to 30 months, to allow women to have a pregnancy, before going back to adjuvant endocrine therapy, to complete the 5 to 10 years of treatment. Very soon, we will hear the safety result from this trial, and we will provide better counsel for those patients that do not want to wait or cannot wait too long to have a pregnancy, because of their age.

The main message for this case is that the care of breast cancer, in general, is a multidisciplinary care, and this is particularly relevant among young patients, where there are additional age-related issues, including fertility, pregnancy, genetic testing, for example. For all these issues, we need really to collaborate with other colleagues, including gynecologists, for not only fertility preservation strategies and pregnancy counseling, but also, for example, to manage other gynecological related issues including contraception, sexual dysfunction, and all the gynecological toxicity of adjuvant endocrine therapy.

Source

Lambertini, M. Challenging Case - Breast Cancer. Presented at Great Debates & Updates in Women's Oncology; Sep 21-23, 2022; Virtual.