HR Management + mBC: Key Prognostic Factors

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Andrew D. Seidman, MD: Nick, we’re talking about positive hormone receptors HER2-negative breast cancer almost like a large category of patients – in fact, it’s the biggest slice of the breast cancer pie. But it is clear that there is heterogeneity, not only as we have discussed in terms of molecular characteristics, but also clinical characteristics. How do you see the management of this population based on other characteristics, endocrine resistance and visceral involvement?

Nicholas McAndrew, MD, MSCE: Absolutely. This is a really important question. First of all, I want to end another discussion on how to deal with patients with a ESR1 mutation, especially since MONALEESA-3 has first-line data, since the endocrine partner in this study was fulvestrant. This may not necessarily be actionable, but it would potentially prompt you to choose fulvestrant as your first-line endocrine partner with a CDK4 / 6 inhibitor as the partner. Especially since a subset analysis of MONALEESA-3 in patients with other activating mutations showed that approximately 14% of patients had ESR1 mutations. Patients, regardless of any of these mutations found, have shown benefit with the addition of ribociclib to fulvestrant. It is important to be at the baseline for a number of reasons.

In terms of other more clinical prognostic factors, menopausal status would certainly determine your choice of the backbone of endocrine therapy. But it is also important to determine whether the patient has de novo disease or recurrent disease. What was their disease-free interval? In previous adjuvant therapy, did they progress on endocrine therapy or did they have a long disease-free interval after completing adjuvant endocrine therapy? Or were they totally de novo from the start? I am also thinking of the tumor burden of the patient and the sites of the disease. Finally, I highly consider their performance status and their ability to adhere to different types of therapies.

The presence of visceral metastases and visceral seizures was one of the most important issues that motivated the decision to choose endocrine therapy combined with molecular therapy over chemotherapy. It is recommended in patients with visceral crisis who present with organ dysfunction due to their visceral metastases, but you may still consider chemotherapy. Emerging data show that the overall response rate is comparable, if not better, in patients receiving a combination of hormone therapy and a CDK4 / 6 inhibitor. As noted in the Young-PEARL study, there was a slightly better overall response rate in patients who received the AI ​​ovarian suppression combination [aromatase inhibitor] plus a CDK inhibitor compared to capecitabine. Even in patients who have visceral metastases that may not be in crisis, I would still consider using the combination regimen.

Andrew D. Seidman, MD: This is an excellent observation. We have all been able to recalibrate our thinking about endocrine therapy versus chemotherapy in the context of visceral disease in the era of CDK4 / 6 inhibitors.

Transcription edited for clarity


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