Abstract PS17-05: Relationship between body mass index and tumor subtype by menopausal status: An analysis in women with lobular carcinoma of the breast
Authors: Rothschild Harriet , Esserman Laura , Benz Christopher , Mukhtar Rita 
Published: February 2021

Background: Invasive lobular carcinoma (ILC) is the second most common type of breast cancer and is primarily estrogen receptor (ER)-positive. Compared to invasive ductal carcinoma, ILC is more strongly associated with risk factors that modulate sex steroid hormones, including obesity and use of hormone replacement therapy. Studies also suggest that body mass index (BMI) and metabolic syndrome may impact the molecular characteristics of ILC. We evaluated the relationship between BMI, metabolic syndrome, and tumor characteristics by menopausal status in a single institution cohort of women with newly diagnosed ILC.

Methods: We retrospectively evaluated ILC cases from an institutional database of patients treated between 1996 and 2020. We excluded cases with mixed ILC/IDC histology, and those with triple negative or human epidermal growth factor-2 overexpressing disease. BMI was calculated as (weight kg)/(height m)^2 and was evaluated continuously and categorically with 20-24.9 as normal weight, 25-30 as overweight, and &gt;30 as obese. Metabolic syndrome was defined as having any 3 of the following 5 factors: obesity, hypertension, hypercholesterolemia, hypertriglyceridemia, or diabetes mellitus. Oncotype Dx Recurrence Scores (RS) were recorded in the subset for whom scores had been obtained clinically. Data were analyzed in Stata 14.2.

Results: Of the 481 ILC cases studied, 147 (30.5%) were pre-menopausal at diagnosis, while 334 (69.5%) were post-menopausal, with mean ages of 48 and 64.9 years (p&lt;0.0001). Most tumors (79.5%) were both ER-positive and progesterone receptor (PR)-positive. Post-menopausal women had significantly more ER-positive/PR-negative ILC than premenopausal women (25.3% vs 9.9%, p&lt;0.001), were more likely to have a BMI in the overweight/obese category (53.6% vs 40.1%, p=0.016), and were more likely to have metabolic syndrome (21.9% vs 6.8%, p&lt;0.001). Of the 143 cases with an Oncotype RS, 69.9% were intermediate, 21.7% were low, and 8.4% were high risk. Post-menopausal women had significantly higher RS than premenopausal women when RS was treated as a continuous variable (16.9 vs 13.8, p=0.007). Among postmenopausal women, overweight/obesity status was associated with lower RS while those with normal weight had a greater proportion of high RS tumors (p=0.027). There was no association between BMI and RS in the pre-menopausal population. Similarly, there was no association between metabolic syndrome and tumor subtype in either group.

Conclusions: In this cohort of women with ER-positive pure ILC, we found that post-menopausal ILC had higher rates of overweight/obesity, metabolic syndrome, and numerically higher RS than pre-menopausal ILC. However, within the post-menopausal group, higher BMI was anti-correlated with RS whereas BMI had no impact on pre-menopausal ILC RS. Since obesity is associated with worse outcomes for breast cancer, these findings are unexpected and raise the possibility that the hormonal pathogenesis and estrogenic drive behind ILC differs in pre- vs post-menopausal women, consistent with their different PR positivity rates, possibly due to the more local production of estrogen from higher breast adiposity in post-menopausal women relative to the greater systemic ovarian production of estrogen in pre-menopausal women. These findings have potential implications for both ILC prevention and adjuvant therapy strategies.

CharacteristicsPremenopausal (n=147)Postmenopausal (n=334)P valueAge, mean (SD)48 (5.5)64.9 (9.7)&lt;0.0001Body mass index0.016BMI&lt;25, n (%)88 (59.9%)155 (46.4%)BMI 25-30, n (%)39 (26.5%)105 (31.4%)BMI&gt;30, n (%)20 (13.6%)74 (22.2%)Metabolic syndrome present, n (%)10 (6.8%)73 (21.9%)&lt;0.001ILC StageNSI, n (%)86 (58.9%)224 (68.3%)II, n (%)40 (27.4%)61 (18.6%)III, n (%)20 (13.7%)43 (13.1%)ILC GradeNS1, n (%)49 (34.3%)93 (28.3%)2, n (%)88 (61.5%)222 (67.5%)3, n (%)6 (4.2%)14 (4.2%)Hormone Receptor Status&lt;0.001ER+/PR+128 (90.1%)236 (74.7%)ER+/PR-14 (9.9%)80 (25.3%)21-gene Recurrence Score in women with BMI&lt;250.020Low, n (%)10 (25%)2 (6%)Intermediate, n (%)28 (70%)24 (72.7%)High, n (%)2 (5%)7 (21.3%)21-gene Recurrence Score in women with BMI&gt;25NSLow, n (%)6 (28.5%)11 (26.8%)Intermediate, n (%)15 (71.5%)27 (65.9%)High, n (%)0 (0%)3 (7.3%)SD, standard deviation, NS, not significant.

Citation Format: Harriet Rothschild, Laura Esserman, Christopher Benz, Rita Mukhtar. Relationship between body mass index and tumor subtype by menopausal status: An analysis in women with lobular carcinoma of the breast [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS17-05.