Breast Cancer : Episode 23

Case 1: Approach to Early Stage, HER2+ Breast Cancer


Tiffany Traina, MD: At my institution we routinely will check HER2 status based on immunohistochemistry as our first screen. And in those select cases that score as 2+ we reflexively do FISH [fluorescence in situ hybridization] testing thereafter.

And the definition of HER2 positivity or amplification that we follow aligns with the ASCO/CAP [American Society of Clinical Oncology/College of American Pathologists] modified guidelines for HER2 positivity.

This particular patient had a tumor larger than 2 cm, and she happened to have node-positive disease. At my institution either of those criteria would select for a patient that we would recommend neoadjuvant therapy in the setting of early stage HER2-positive disease.

Once we’ve made the decision to deliver neoadjuvant therapy my preference is often dose dense AC [doxorubicin/cyclophosphamide] followed by weekly paclitaxel, with trastuzumab and pertuzumab. Evidence from APHINITY would suggest TCHP [docetaxel, carboplatin, trastuzumab, pertuzumab] is also a supported regimen.

What I often will do is plan to continue the dual HER2-targeted therapy in the adjuvant setting to continue out a year. Although recently the KATHERINE data would suggest that there is a benefit to refining our adjuvant treatment, at least in terms of HER2-targeted therapy based on the results of surgery and the response to neoadjuvant therapy.

When patients achieve a pathologic complete response, I continue the trastuzumab and pertuzumab doublet to finish out a year. However, in those patients who failed to achieve a pathologic complete response, the KATHERINE data would support using T-DM1 [trastuzumab emtansine] for the remainder of the year, and that is based on almost a 50% improvement in invasive disease-free survival when making that change from trastuzumab-based regimen to [trastuzumab emtansine].

In the adjuvant setting following neoadjuvant therapy, the treatment choice is largely dictated by whether somebody has achieved the pathologic complete response. And the KATHERINE data that were presented and published recently are what has informed that treatment recommendation.

In patients who were deemed to be high risk enough to warrant neoadjuvant therapy, even in the setting where they may be node negative but had a large tumor size, our practice would be to continue trastuzumab and pertuzumab to finish out a year, if that patient achieved a pathologic complete response.

However, if they failed to have the pathologic complete response, the KATHERINE data would support switching to [trastuzumab emtansine] in the adjuvant setting for that year of therapy.

KATHERINE supports the use of [trastuzumab emtansine], based on both about a 50% improvement in disease-free survival or invasive disease-free survival and almost a 40% improvement in a distant recurrence. So those are meaningful end points, and I think that the KATHERINE data have really been practice changing.

The use of neratinib in the extended adjuvant setting is based on data from the ExteNET study. We have to remember that this is a trial that began several years ago, almost predating our current utilization of pertuzumab in the adjuvant setting.

That trial demonstrated an improvement in the use of 1 year of neratinib following 1 year of adjuvant trastuzumab therapy for patients with HER2-positive early stage breast cancer. The benefit in disease-free survival was really limited to the subset of patients who had hormonally driven disease. I think that we are left to extrapolate whether there would be a benefit to using neratinib in the extended adjuvant setting now, when our practice is incorporating pertuzumab and even, potentially, [trastuzumab emtansine].

We don’t have those data in terms of efficacy. We do have some safety data from other post-approval trials, and I would say that I consider the use of neratinib in the extended adjuvant setting for my highest-risk patients who have ER-positive, HER2-positive breast cancer, node-positive disease. And I entertain the discussion of using neratinib as we’re approaching the end of that 1 year of adjuvant HER2-based treatment.

Transcript edited for clarity.

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