Treatments for HR+, HER2-Negative Metastatic Breast Cancer

Debu Tripathy, MD:The new guidelines, or recently revised guidelines, for hormone receptor—positive and HER2-negative advanced breast cancer reflect some of the new findings in biological therapies. Importantly, it is felt that any patient with hormone-sensitive disease should be tried for hormonal therapy as initial treatment. Now, there are some exceptions to this: patients who have very rapidly progressing disease, who have visceral and bulky disease that may be symptomatic, or who have what’s called visceral crisis. For those patients, it’s still felt that induction chemotherapy might be most appropriate. Then, if they do have a response, move them on to endocrine therapy. But the vast majority of patients are felt to be candidates for endocrine therapy first.

I would add, as my own editorial comment, that patients with low estrogen-receptor expression do tend to have a lower response. Under 10%, we typically start off with chemotherapy at our center. But having said that, the first approach for patients would be some form of endocrine therapy, and it’s also been felt that in patients who were premenopausal…ovarian blockade should accompany this.

With the advent of the biological drugs, the guidelines have reflected the fact that they have not been associated with a survival advantage. They actually give you the option to use an aromatase inhibitor either alone or with a CDK inhibitor as first-line therapy. And then, a second-line therapy, fulvestrant, is typically used. This can also be given with a CDK inhibitor if it hasn’t been used previously, or everolimus or exemestane with everolimus. These are all acceptable second-line agents. But again, with the biological agents not having produced a survival advantage and having some side effects, it’s felt that one can go with endocrine therapy alone or with biotherapy.

I’ll tell you that in our practice, we generally do combine a treatment with biotherapy, certainly with CKD4/6 inhibitors in the first line. After that, when patients are refractory to hormonal therapy, then we move on to chemotherapy. The point at which you do that or at which you say someone is resistant really goes by the patient’s clinical status. Some amount of clinical judgment has to be used there.

For hormone receptor-positive and HER2-negative breast cancer, the level 1 evidence points to the use of an aromatase inhibitor and ovarian suppression if the patient is premenopausal. The use of CDK4/6 inhibitors is recommended as first-line therapy on the basis of clear improvement in PFS. However, one could consider endocrine therapy alone, particularly in someone who may not be able to travel regularly and may be at risk of complications of neutropenia. But keep in mind, we have not yet identified clinical or biological factors that can reliably tell us who will and will not benefit from a CDK4/6 inhibitor. The same goes for everolimus.

Transcript edited for clarity.