L1CAM Expression in Recurrent Estrogen Positive/HER2 Negative Breast Cancer: A Novel Biomarker Worth Considering.

We investigate L1 cell adhesion molecule (L1CAM) expression in estrogen receptor (ER)-positive/human epidermal growth factor receptor (HER2)-negative breast carcinomas. The finding of a potential correlation between high L1CAM expression and recurrent/metastatic disease in luminal A and B breast carcinomas may be helpful for risk stratification and open opportunities for targeted therapies. 304 cases comprising 152 cases of ER-positive, progesterone receptor (PR)-positive/negative, and HER2-negative recurrent/metastatic breast carcinomas and 152 nonrecurrent controls were included. ER, PR, HER-2, Ki-67 status, Nottingham grade, tumor size, tumor stage, number of foci, lymph node status, lymphovascular invasion, phenotype, laterality, age at diagnosis and first distant or local recurrence were recorded. L1CAM positive cases showed increased specificity for recurrence and these patients were significantly younger than L1CAM negative ones. Compared with L1CAM negative recurrent cases, L1CAM positive ones had a noticeably higher Ki-67, tended to be larger and recurred sooner. All L1CAM positive recurrent/metastatic cases were of the luminal B subtype compared with 67.3% of the L1CAM negative cases. L1CAM is highly specific for recurrence in a subset of breast cancer patients and may be associated with more aggressive behavior, particularly in luminal B breast cancers with higher Ki-67 expression. Further investigation about the prognostic value of L1CAM is warranted.

Frequency, Clinicopathologic Characteristics, and Follow-up of HER2-Positive Nonpleomorphic Invasive Lobular Carcinoma of the Breast.

OBJECTIVES: To investigate human epidermal growth factor receptor 2 (HER2)-positive nonpleomorphic invasive lobular carcinoma (ILC), which has rarely been addressed. METHODS: Clinicopathologic characteristics and follow-up of HER2-positive nonpleomorphic ILCs were collected and compared to those of HER2-negative counterparts. RESULTS: Twenty-one cases of HER2-positive nonpleomorphic ILCs were identified, 6.3% of the study population. Compared to HER2-negative nonpleomorphic ILC, patients with HER2 positivity were older (P < .05), likely to be hormonal receptor negative (P < .01), and had higher histologic grade and angiolymphatic invasion (P < .01). HER2 positivity in nonpleomorphic ILCs was associated with higher recurrence/metastasis with hazard ratio of 2.03 (P < .05). No patient who received neoadjuvant therapy achieved pathologic complete response, and HER2-targeted therapy tended to reduce recurrence/metastasis in patients with HER2-positive nonpleomorphic ILC. CONCLUSIONS: Our results highlight the existence of HER2 positivity in nonpleomorphic ILCs and reinforce that HER2 is associated with worse prognosis in nonpleomorphic ILC.

Second-harmonic generation directionality is associated with neoadjuvant chemotherapy response in breast cancer core needle biopsies.

Neoadjuvant chemotherapy (NACT) is routinely administered to subsets of breast cancer patients, including triple negative (TN) or human epidermal growth factor receptor 2-positive (HER2+) cancers. After NACT and subsequent surgical resection, 5% to 30% of patients have no residual invasive carcinoma, termed pathological complete response. Unfortunately, many patients experience little-to-no response after NACT and unnecessarily suffer its side effects. Methods are needed to predict an individual patient's response to NACT. Core needle biopsies, taken before NACT, consist of tumor cells and the surrounding extracellular matrix. We performed second-harmonic generation (SHG) imaging of fibrillar collagen in core needle biopsy sections as a possible predictor of response to NACT. The ratio of forward-to-backward scattering (F/B) SHG was assessed in the "tumor bulk" and "tumor­host interface" in HER2+ and TN core needle biopsy sections. Patient response was classified post-treatment using the Residual Cancer Burden (RCB) score. In HER2+ biopsies, RCB class was associated with F/B derived from the tumor­stromal interface, but not tumor bulk. F/B was not associated with RCB class in TN biopsies. These findings suggest that F/B from needle biopsy sections may be a useful predictor of which patients will respond favorably to NACT, with the potential to help reduce overtreatment.