PURPOSE: Recent guidelines defined a new reporting category of ER-low-positive breast cancer based on immunohistochemistry (IHC). While low positivity of either hormone receptor is uncommon in invasive lobular carcinoma (ILC), we sought to investigate whether relatively low hormone receptor positivity was associated with tumor characteristics and patient outcomes in a single institutional cohort. METHODS: We searched an institutional database for cases of stage I-III ILC with available IHC reports. Based on prior published categories in ILC, ER was classified as low, medium, or high as defined by ER staining of 10-69%, 70-89%, and ≥ 90% respectively. PR low and high tumors were defined by < 20%, or ≥ 20% staining respectively. We used chi-squared tests, t-tests, and Cox proportional hazards models to evaluate associations between ER/PR categories and tumor characteristics or disease-free survival (DFS). RESULTS: The cohort consisted of 707 ILC cases, with 11% of cases categorized as ER low, 15.1% as medium, and 73.8% as high. The majority (67.6%) were PR high. Patients with ER low/medium expression were significantly younger, and more likely to also have PR low and/or HER2 positive tumors compared to those that were ER high. In a Cox proportional hazards model adjusting for age, stage, grade, pleomorphic histology, and treatment, ER category was not prognostic for DFS, but PR negative and PR low status each had significantly worse DFS compared to PR high status (HR 3.5, 95% CI 1.8-6.7, p < 0.001; and HR 2.0, 95% CI 1.1-3.5, p = 0.015, respectively). CONCLUSION: These findings highlight the relevance of quantifying ER and PR within ILC.

Purpose

HER2 overexpression has a central role in breast cancer carcinogenesis and is associated with poor prognosis if untreated. Lately, identification of HER2-low breast cancer has been proposed to select patients for novel HER2-directed chemotherapy and includes cancers with immunohistochemistry 1 + or 2 + with negative FISH, encompassing approximately 55-60% of all breast carcinomas. In early-stage breast cancer, the prognostic significance of HER2 low-disease is less well understood, with a particular paucity of data evaluating the prevalence and implications of HER2-low status in invasive lobular carcinoma (ILC).

Methods

We evaluated 666 stage I-III ILC tumors from a prospectively maintained institutional database, comparing clinicopathologic features and disease-free survival (DFS) using a multivariable Cox proportional hazards model.

Results

HER2-low status was common in this cohort of patients with ILC, but most clinicopathologic features did not differ between HER2-low and HER2-negative cases. However, when adjusting for tumor size, number of positive nodes, ER/PR status, and local therapy received, patients with HER2-low status had worse disease-free survival (DFS) than those with HER2-negative tumors (hazard ratio 2.0, 95% confidence interval 1.0-4.1, p = 0.05).

Conclusion

This difference in DFS supports the notion that HER2-low and HER2-negative early stage ILC may differ clinically, despite similar clinicopathologic features. Further investigation into the potential benefit of HER2 targeted therapy in HER2-low early-stage breast cancer, and specifically lobular cancer, is warranted to ensure optimal outcomes in this distinct tumor subtype.

Purpose

We investigated the relationship between obesity, menopausal status, and invasive lobular carcinoma (ILC), the second most common histological subtype of breast cancer. Specifically, we evaluated the association between body mass index (BMI), metabolic syndrome, the 21-gene Oncotype Recurrence Score (Oncotype RS), and pathological features in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor-2-negative ILC.

Methods

The study cohort included 491 patients from a prospectively maintained institutional database consisting of patients with stage I-III, HR-positive ILC who underwent surgical treatment between 1996 and 2019.

Results

Contrary to our expectations, we found that lower BMI was significantly associated with having higher Oncotype RS (18.9% versus 4.8%, p = 0.028) in post-menopausal patients, but was not related to tumor characteristics in pre-menopausal patients. Multivariate network analyses suggested a strong relationship between post-menopausal status itself and tumor characteristics, with lesser influence of BMI.

Conclusion

These findings provide further insight into the recently appreciated heterogeneity within ILC and support the need for further investigation into the drivers of this disease and tailored treatment strategies.

Background

Although investigators have shown associations between socioeconomic status (SES) and outcomes in breast cancer, there is a paucity of such data for invasive lobular carcinoma (ILC), the second most common type of breast cancer. Herein we evaluated the relationship between SES with tumor features and outcomes in stage I to III patients with ILC.

Methods

We analyzed a prospectively maintained institutional ILC database and utilized the area deprivation index (ADI) to determine neighborhood adversity, an indicator of SES. We used Cox proportional hazards models in Stata 17.0 to evaluate relationships between ADI quintile (Q), race, body mass index (BMI), clinicopathologic features, treatment type, and event-free survival (EFS).

Results

Of 804 patients with ILC, 21.4% lived in neighborhoods classified as ADI Q1 (least resource-deprived) and 19.7% in Q5 (most resource-deprived). Higher deprivation was significantly associated with larger tumor size (3.6 cm in Q5 vs. 3.1 cm in Q1), increased presence of lymphovascular invasion (8.9% in Q5 vs. 6.7% in Q1), and decreased use of adjuvant endocrine therapy (67.1% in Q5 vs. 73.6% in Q1). On multivariable analysis, tumor size, receptor subtypes, and omission of adjuvant endocrine therapy were associated with reduced EFS.

Conclusions

These data show that patients with ILC and higher ADI experience more aggressive tumors and differences in treatment. More data evaluating the complex relationships between these factors is needed to optimize outcomes for patients with ILC, regardless of SES.

Impact

ADI is associated with differences in patients with ILC.