Understanding PARP Inhibition in BRCA-Mutated Breast Cancer - Episode 2

Considering Treatment for HER2-Negative Breast Cancer


Joyce A. O’Shaughnessy, MD: For HER2-negative breast cancer, there are 2 main types: estrogen receptor [ER]—positive, hormone receptor–positive, HER2-negative; and then triple-negative breast cancers. For triple-negative breast cancer, because we don’t have the estrogen receptor to aim at or HER2 to aim at, chemotherapy is the standard of care right now both in the curative setting for early stage breast cancer and for metastatic disease.

For estrogen receptor—positive, HER2-negative patients, antiestrogen therapy — so-called endocrine therapy or hormonal therapy — is really the mainstay. You’re really aiming at the key driver of that breast cancer, the estrogen receptor. It is almost always the case that whether it be in the curative setting or in the metastatic setting, inhibiting that estrogen receptor is the most important therapy of all. Oftentimes in the metastatic setting, we combine hormonal therapy with other blockers of cell division, such as the CDK4/6 [cyclin-dependent kinases 4 and 6] inhibitors or the mTOR [mammalian target of rapamycin] inhibitors. But it’s all aimed at making inhibition of the estrogen receptor that much more powerful.

Since I’ve been in practice for some decades now, we’ve seen a great evolution in our therapies becoming increasingly targeted. Chemotherapy still plays a very important curative role in some highly proliferative—meaning fast growing—breast cancer. That’s very important. But increasingly, we’re getting the most improvement in outcomes through targeted therapy such as using Herceptin [trastuzumab] against HER2, for example, or antiestrogen therapy, endocrine therapy against the estrogen receptor, combined with novel targeted agents such as the CDK4/6 inhibitors or mTOR inhibitors. Increasingly, we’re using checkpoint inhibitors as well in triple-negative breast cancer. We are seeing, thankfully, less use of chemotherapy in patients as we get better and better targeted therapies. This is happening a lot in metastatic breast cancer that’s estrogen receptor—positive and HER2-negative: less use of chemotherapy and greater use of oral agents that are very highly targeted against ER-positive breast cancer.

Transcript Edited for Clarity