Case Presentation: Localized HER2-Positive Breast Cancer Case Presentation

A 57-year-old postmenopausal woman with no significant past medical history self-palpates a left-sided breast mass and presents for evaluation. Diagnostic mammogram identifies a suspicious 2.1 cm spiculated lesion. She undergoes ultrasound-guided biopsy, which identifies an estrogen receptor (ER)-negative/progesterone receptor (PR)-negative/human epidermal growth factor receptor 2 (HER2)-positive invasive ductal carcinoma.

On clinical exam, she has no palpable lymph nodes. Breast MRI identifies a second left-sided breast lesion, 0.5 cm, as well as a suspiciously enlarged lymph node. These both undergo biopsy, and both are also identified as ER-negative/PR-negative/HER2-positive invasive ductal carcinoma. Review of systems is positive for a 10-pound weight loss. She undergoes a CT of the chest/abdomen/pelvis, which shows no evidence of distant metastatic disease.

TNM staging in multifocal breast cancer is based on the size of the largest tumor, in this case 2.1 cm, which is T2. The single suspicious and biopsy-positive lymph node is N1. Not all cases of localized breast cancer require staging scans, but HER2-positive disease metastatic to the lymph node, particularly with a positive review of systems for weight loss, warrants further staging scans to assess for metastatic disease.

The decision is made to pursue neoadjuvant therapy.

The decision to pursue neoadjuvant therapy is based on several principles.

1. Breast conservation: Neoadjuvant therapy can decrease the size of lesions that may be technically and/or cosmetically challenging to remove via lumpectomy. HER2-positive breast cancer tends to be very responsive to HER2-based therapy, and a decrease in size may make lumpectomy possible where it was not feasible prior.
2. Axillary lymph node down-staging: This patient has a clinical N1 breast cancer. If after neoadjuvant therapy, the sentinel lymph node is negative (ypN0), the patient may not require axillary lymph node dissection.
3. Adaptive approach with T-DM1: The KATHERINE trial (NCT 01772472) showed that patients with residual HER2-positive breast cancer after neoadjuvant therapy were more likely to benefit from changing to the HER2-targeted antibody drug conjugate trastuzumab emtansine (T-DM1). This adaptive treatment plan resulted in a 50% decreased risk of recurrence of invasive breast cancer or death (von Minckwitz et al, NEJM 2018).
4. Other reasons for postponing surgery: These may include but are not limited to other medical issues that may make upfront surgery too high risk.

The patient received docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) every 3 weeks for 6 cycles.

Notably, HER2-positive breast cancer has high rates of pathologic complete response, which is associated with markedly improved event-free survival. Rates are highest in hormone receptor-negative, HER2-positive breast cancer. TCHP is a standard of care neoadjuvant regimen for stage II-III HER2-positive breast cancer (NCT02131064). Patients may also receive a comparable regimen with weekly paclitaxel instead of docetaxel.

Studies have also assessed de-escalation of this regiment to a taxane, trastuzumab, and pertuzumab (THP) and shown favorable pathologic complete responses, with pCR rates from 57% to 90%, highest if the cancer is hormone receptor-negative (NCT03716180, NCT01817452). While neoadjuvant THP is not currently a standard of care, larger clinical trials are currently assessing this regimen given the aforementioned results (NCT04266249).

If this patient were to have had T1N0M0 breast cancer, she may have benefited from upfront surgery followed by adjuvant paclitaxel and trastuzuamb (APT) for 12 weeks followed by 9 months trastuzumab every 3 weeks, per the APT trial (NCT00542451).

Of note, patients receiving trastuzumab-based therapy should undergo baseline and monitoring transthoracic echocardiograms (TTE) while on treatment to monitor cardiac function.

After completing neoadjuvant therapy, she undergoes lumpectomy and is found to have had a complete pathologic response. Sentinel lymph node is also negative, thus final pathologic lymph node stage in ypN0, and no axillary dissection is undertaken. Given the pathologic complete response, she continues on trastuzumab and pertuzumab every 3 weeks to complete a year of therapy.

The efficacy of adding pertuzumab to trastuzumab in the adjuvant setting were shown to result in superior invasive disease-free survival in patients with high-risk localized HER2-positive breast cancer, per the APHINITY trial (NCT01358877). If there were to have been residual disease, she would have been recommended to receive adjuvant trastuzumab emtansine every 21 days for 14 cycles, per the KATHERINE trial (NCT01772472), which showed markedly improved disease-free survival at 3 years compared to trastuzumab-based adjuvant therapy.

She returns for her yearly screening mammogram 1 year after diagnosis and has no evidence of disease. Her heart function remains normal upon completing trastuzumab-based therapy, and she is feeling well.