Targeted Therapy in Early-Stage HER2+ Breast Cancer - Episode 4

Selecting HER2-Targeted Therapy for Early Breast Cancer

Erika P. Hamilton, MD: Let’s talk about optimal patient selection. How do you decide who is going to receive pertuzumab? Who may receive pertuzumab in the adjuvant setting, etc?

Stephanie Graff, MD, FACP: I think in the HER2-positive early stage disease setting, trying to decide how to treat it is critical. I tend to treat most of my patients in the neoadjuvant setting in light of the KATHERINE data, which we’ll get to. Occasionally, patients present having already had surgery, and then we make decisions with the final pathology that we have available to us.

In the neoadjuvant setting, I rely very heavily on our clinical examination and our breast radiology colleagues, breast MRI, and ultrasound to clearly define where we are. I do proceed with needle biopsies of axillary lymph nodes that look abnormal on imaging so that I can clearly define whether this is a person who has known lymph node-positive breast cancer, which I think helps clarify things in terms of surgical approach and radiation options after neoadjuvant chemotherapy, to know if they have nodal involvement or not.

For patients with T2 or larger tumors, or for patients with lymph node-positive breast cancer, I tend to use TCHP—Taxotere [docetaxel], carboplatin, Herceptin [trastuzumab], Perjeta [pertuzumab]—using that dual HER2 approach. For patients with T1N0 breast cancer, I tend to use paclitaxel/trastuzumab, which we’ve seen great long-term outcomes with and less toxicity than we would get with dual chemotherapy, dual HER2-targeted therapy. Honestly, I will even do that in a neoadjuvant approach as well. But I think that how to optimally sequence and identify T1N0 breast cancer is an area of controversy right now in our field, and is probably, in light of the KATHERINE data, a group of patients for whom we need better long-term data on so we can decide how to stratify them. What about you, Dr Hamilton?

Erika P. Hamilton, MD: Absolutely. Clinically, I practice very similar to that. We keep alluding to KATHERINE, and I promise the audience that we’ll eventually get to that, but I think that’s an important point. We don’t have to feel like we have to give a very aggressive regimen up front to somebody who we think is low risk. To be eligible for adjuvant T-DM1 [trastuzumab emtansine] for the KATHERINE trial, you just had to have not had a pathological complete response [pCR] to whatever therapy you were given in the neoadjuvant setting. So, I agree. For older patients or for patients who have very small tumors, I frequently give taxane/trastuzumab. Maybe that’s all that they need. If somebody does not have a pathologic complete response or ends up with more disease at the time of surgery, etc, you’re certainly entitled and able, under that label, to go back and give adjuvant T-DM1 in that space.

Stephanie Graff, MD, FACP: Something neither of us have mentioned yet is that the hormone receptor status does not factor into decision-making here. Whether somebody is an estrogen/progesterone receptor-negative patient or a hormone receptor-expressing patient, in that chemotherapy/HER2/antibody decision-making, that is not a part of my decision. Obviously, for somebody who is expressing hormone receptors, later we add in endocrine therapy. But that doesn’t shape what chemotherapy or HER2 combo I choose.

Erika P. Hamilton, MD: Absolutely. You’re completely right. It does affect what pathologic complete response rate you’re probably anticipating. We know that the patients who also have hormone receptor-positive status tend to have lower pCR rates. But across multiple trials, whether it’s pertuzumab or T-DM1, TCHP [docetaxel, carboplatin, trastuzumab, pertuzumab] versus TCH [docetaxel, carboplatin, trastuzumab], the benefit of those is not less for ER [estrogen receptor]-positive patients.

Transcript edited for clarity.