The patient can be offered 1 of 2 adjuvant treatment regimens, either TH or TCH (Table 2). Since the patient had lumpectomy, she is an appropriate candidate for adjuvant radiation, which would be started after completion of the chemotherapy backbone (taxane/platinum). Endocrine therapy for at least 5 years should be offered sequentially or concurrently with radiation. Her long-term prognosis is very favorable.
Case Patient 2
A 43-year-old woman presents with a 4-cm breast mass, a separate skin nodule, and palpable matted axillary lymphadenopathy. Biopsies of the breast mass and subcutaneous nodule reveal invasive ductal carcinoma that is ER-negative, PR-negative, and HER2-positive by IHC (3+ staining). Based on clinical findings, the patient is staged as T4b (separate tumor nodule), N2 (matted axillary lymph nodes). Systemic staging with CT scan of the chest, abdomen, and pelvis shows no evidence of distant metastases.
What is the recommended approach to management for this patient?
Recommendations for neoadjuvant therapy, given before definitive surgery, follow the same path as with other subtypes of breast cancer. Patients with suspected anatomical stage III disease are strongly encouraged to undergo upfront (neoadjuvant) chemotherapy in combination with HER2-targeted agents. In addition, all HER2-positive patients with clinically node-positive disease can be offered neoadjuvant therapy using chemotherapy plus dual anti-HER2 therapy (trastuzumab and pertuzumab), with complete pathological response expected in more than 60% of patients.26,27 Because this patient has locally advanced disease, especially skin involvement and matted axillary nodes, she should undergo neoadjuvant therapy. Preferred regimens contain both trastuzumab and pertuzumab in combination with cytotoxic chemotherapy. The latter may be given concurrently (nonanthracycline regimens, such as docetaxel plus carboplatin) or sequentially (anthracycline-based regimens), as outlined in Table 2. Administration of anthracyclines and trastuzumab simultaneously is contraindicated due to increased risk of cardiomyopathy.28
Endocrine therapy is not indicated for this patient per the current standard of care because the tumor was ER- and PR-negative. Had the tumor been hormone receptor–positive, endocrine therapy for a minimum of 5 years would have been indicated. Likewise, in the case of hormone receptor–positive disease, 12 months of neratinib therapy after completion of trastuzumab may add further benefit, as shown in the ExteNET trial.22,23 Neratinib seems to have a propensity to prevent or delay trastuzumab-induced overexpression of estrogen receptors. This is mainly due to hormone receptor/HER2 crosstalk, a potential mechanism of resistance to trastuzumab.29,30
In addition to the medical therapy options discussed here, this patient would be expected to benefit from adjuvant radiation to the breast and regional lymph nodes, given the presence of T4 disease and bulky adenopathy in the axilla.31
Case 2 Conclusion
The patient undergoes neoadjuvant treatment (docetaxel, carboplatin, trastuzumab, and pertuzumab every 21 days for a total of 6 cycles), followed by surgical resection (modified radical mastectomy) that reveals complete pathological response (no residual invasive carcinoma). Subsequently, she receives radiation therapy to the primary tumor site and regional lymph nodes while continuing trastuzumab and pertuzumab for 11 more cycles (17 total). Despite presenting with locally advanced disease, the patient has a favorable overall prognosis due to an excellent pathological response.
What is the approach to follow-up after completion of primary therapy?
Patients may follow up every 3 to 6 months for clinical evaluation in the first 5 years after completing primary adjuvant therapy. An annual screening mammogram is recommended as well. Body imaging can be done if dictated by symptoms. However, routine CT, positron emission tomography, or bone scans are not recommended as part of follow-up in the absence of symptoms, mainly because of a lack of evidence that such surveillance improves survival.32
