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HER2+ EBC: Evolution

CE / CME

The Evolving Therapeutic Landscape for HER2-Positive Early-Stage Breast Cancer

Pharmacists: 1.00 contact hour (0.1 CEUs)

Physicians: Maximum of 1.00 AMA PRA Category 1 Credit™

Nurses: 1.00 Nursing contact hour

Released: August 10, 2020

Expiration: August 09, 2021

Lee Schwartzberg
Lee Schwartzberg, MD
CME/CE Information

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Proposed Strategy for Managing Patients With Stage I-III HER2-Positive EBC

Based on the data discussed above, this is a proposed strategy for managing patients with stage I-III HER2-positive EBC. The middle box represents a relatively common scenario: clinically T1c, N0 with HER2 positivity. These patients often are diagnosed with breast cancer through screening tests such as mammograms, and only occasionally have symptoms that result in diagnosis. For this group, risk assessment and decision making guided by patient preference is very important. Treatment decisions for these patients can generally follow 1 of 2 directions: surgery followed by adjuvant therapy similar to those with cT1a/b tumors (if not high risk) or neoadjuvant therapy followed by surgery similar to patients with ≥ cT2 tumors.

For patients with very small tumors (cT1a, N0), surgery followed by observation may be appropriate. For these patients as well as those with T1b disease the combination of trastuzumab and paclitaxel, followed by trastuzumab to complete 1 full year after surgery, as was shown in the APT study, could be considered

Patients with larger tumors, ie, clinical stage II (cT2 or clinically node positive), should be strongly considered for neoadjuvant treatment based on the proven benefit of neoadjuvant chemotherapy plus trastuzumab and pertuzumab. Following a course of neoadjuvant therapy, patients who achieve a pCR (no residual tumor in breast or lymph nodes) and are hormone receptor negative can receive trastuzumab, with or without pertuzumab, to complete 1 year of therapy. If they are hormone receptor positive, neratinib should also be considered as extended adjuvant therapy after completing 1 year of anti-HER2 antibody therapy (trastuzumab with or without pertuzumab).

Patients who received standard optimal neoadjuvant therapy but still have residual invasive disease are at the highest risk for relapse and should receive T-DM1 to complete a year of therapy. If they were hormone receptor positive at diagnosis, subsequent neratinib should be strongly considered.

In short, maximally aggressive treatment (including neratinib) is appropriate for patients who have clinical stage IIb or III cancers before receiving neoadjuvant treatment, and who have residual cancer burden after surgery.

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A 48-year-old woman presents with clinical cT1cN0M0 breast cancer. Testing reveals ER positive of 90%, PgR positive of 80%, Ki-67 of 50%, and HER2 3+ by IHC, HER2/neu by FISH amplification positive. Lumpectomy and sentinel lymph node biopsy revealed a 2.6-cm ER/PgR–positive, HER2-positive breast cancer. Two of 3 sentinel lymph nodes (LNs) were positive disease, with the largest LN deposit being an 8-mm metastasis.

In your current clinical practice, in addition to standard endocrine therapy, what adjuvant chemotherapy would you recommend for this patient?

Our 48-year-old woman with clinical cT1cN0M0 breast cancer underwent lumpectomy and sentinel lymph node biopsy, which revealed a 2.6-cm ER/PgR-positive, HER2-positive breast cancer. Two of 3 sentinel LNs were positive disease with the largest LN deposit being an 8-mm metastasis. Following surgery, she was treated with adjuvant docetaxel/carboplatin/trastuzumab/pertuzumab plus endocrine therapy.

In your current clinical practice, what would you recommend after the patient completes chemotherapy?

A 51-year-old woman presents with cT2cN1M0 disease that was hormone receptor negative (by IHC) and HER2 positive (by FISH). She received neoadjuvant AC→THP followed by surgery. At surgery, she is found to have residual disease in her breast (1 cm) and LN (1 of 12 LN with 1.2-cm focus). The residual disease remains hormone receptor negative and HER2 positive.

In your current clinical practice, what adjuvant therapy would you recommend for this patient?
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