Meet The Professors Breast Vol 7, Issue 1

Tracks 2

DR LOVE: Sandy, the cardiologist recommended treating the patient’s cardiomyopathy and felt she could receive a trastuzumab-based therapy as long as she did not also receive an anthracycline. How do you feel about that recommendation?

DR SWAIN: I agree with the cardiologist. While the data are limited, Dr Yu at MD Anderson examined patients who had received trastuzumab and were then treated for abnormal ejection fractions. He found they could be re-treated with trastuzumab. I believe a trastuzumab-containing regimen would be the best choice with regard to benefit and that his work supports that approach.

I would treat her with a TCH regimen preoperatively, and I would expect a good clinical response if not a pathologic complete response (pCR), considering the data for neoadjuvant trastuzumab-containing regimens. In the NOAH trial, the pCR rate was approximately 40 percent for patients who received neoadjuvant chemotherapy and trastuzumab (Gianni 2008; [1.1]). Also, in Dr Buzdar’s neoadjuvant trial, paclitaxel followed by FEC/trastuzumab resulted in pCR rates in the 50 to 60 percent range (Buzdar 2007; [1.2]).

DR LOVE: Cliff, how would you treat this patient?

DR HUDIS: She’s not a great candidate for any cytotoxic chemotherapy. From an evidence-based point of view, I believe TCH is the only option, so that’s what I would use.

The CALGB has a preoperative trial randomly assigning patients to trastuzumab, lapatinib or both drugs, all with weekly paclitaxel (CALGB-40601). They are evaluating responses in the breast, so the patients go off study at the time of surgery. The recommendation then is for dose-dense AC, followed by finishing a year with trastuzumab, and we are using that approach for patients with larger primary tumors.

I believe that the important question may not be whether these patients need an anthracycline but rather how much chemotherapy they need at all. With trastuzumab, much of our debate about specific chemotherapy regimens may be muted — the trastuzumab effect may be a great leveler.

DR LOVE: Dr Tracy, how did you treat the patient?

DR TRACY: We administered the full regimen of TCH, and the mass shrank clinically and on imaging. She also received cardiac medication and her echocardiogram steadily improved to about 60 percent. She opted for mastectomy, and pathology revealed a 2.3-cm infiltrating ductal cancer with some high-grade DCIS and two positive nodes out of 22.

She then received radiation therapy and began an aromatase inhibitor. It’s been four years now, and she is faring well with no evidence of disease and an ejection fraction of 60 percent with only minimal maintenance cardiac medication.

DR LOVE: Cliff, what are some of the promising new approaches to anti-HER2 treatment?

DR HUDIS: This is a remarkably exciting area. We should take great pride in the translational science that has allowed us to understand a target and build appropriate drugs rather than discover them empirically.

We have trial evidence that anti-HER2 drugs such as lapatinib and trastuzumab can be combined, including Dr O’Shaughnessy’s study in which patients with HER2-positive metastatic breast cancer previously treated with multiple lines of trastuzumab-containing therapy were randomly assigned to lapatinib with or without trastuzumab (O’Shaughnessy 2008). She reported a modest benefit for the combination, which people use to support continuing trastuzumab and using the combination (1.3).

DR LOVE: What about the strategy of continuous biologic blockade?

DR HUDIS: The German group conducted a trial that essentially duplicated the pivotal capecitabine/lapatinib study except with trastuzumab in place of lapatinib (von Minckwitz 2008). These patients had HER2-positive metastatic disease progressing on trastuzumab and, remarkably, the time to progression was longer with the combination and the response rate was about 50 percent (1.4).

This study was closed early because of accrual problems related to the availability of lapatinib. Nevertheless, it provided this robust signal of activity. Does this mean that we should continue trastuzumab as we cycle through therapies for patients? That is still difficult to answer. Some patients probably do respond to continued anti-HER2 therapy, but some patients probably do not.

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