Etiology of hormone receptor positive breast cancer differs by levels of histologic grade and proliferation

Abstract

Limited epidemiological evidence suggests that the etiology of hormone receptor positive (HR+) breast cancer may differ by levels of histologic grade and proliferation. We pooled risk factor and pathology data on 5,905 HR+ breast cancer cases and 26,281 controls from 11 epidemiological studies. Proliferation was determined by centralized automated measures of KI67 in tissue microarrays. Odds ratios (OR), 95% confidence intervals (CI) and p‐values for case–case and case–control comparisons for risk factors in relation to levels of grade and quartiles (Q1–Q4) of KI67 were estimated using polytomous logistic regression models. Case–case comparisons showed associations between nulliparity and high KI67 [OR (95% CI) for Q4 vs. Q1 = 1.54 (1.22, 1.95)]; obesity and high grade [grade 3 vs. 1 = 1.68 (1.31, 2.16)] and current use of combined hormone therapy (HT) and low grade [grade 3 vs. 1 = 0.27 (0.16, 0.44)] tumors. In case–control comparisons, nulliparity was associated with elevated risk of tumors with high but not low levels of proliferation [1.43 (1.14, 1.81) for KI67 Q4 vs. 0.83 (0.60, 1.14) for KI67 Q1]; obesity among women ≥50 years with high but not low grade tumors [1.55 (1.17, 2.06) for grade 3 vs. 0.88 (0.66, 1.16) for grade 1] and HT with low but not high grade tumors [3.07 (2.22, 4.23) for grade 1 vs. 0.85 (0.55, 1.30) for grade 3]. Menarcheal age and family history were similarly associated with HR+ tumors of different grade or KI67 levels. These findings provide insights into the etiologic heterogeneity of HR+ tumors.

Breast cancer risk factors, survival and recurrence, and tumor molecular subtype: analysis of 3012 women from an indigenous Asian population

“…We categorized risk factors based on what is the convention for each variable and in accordance with what has been published in large-scale studies of breast cancer [ 18 , 26 ]. We categorized age at menarche [≤12 years (early menarche), 13, 14 and ≥ 15 years (late menarche)]; family history of breast cancer in a first-degree relative [yes and no]; age at FFP [< 21, 21–24.9, 25–30, > 30 years] and age at menopause [≤ 50 and > 50 years] similarly as in previously published articles [ 18 , 26 ]. For BMI, we adopted the World Health Organization classification [< 18.5 kg/m 2 (underweight); 18.5–24.9 kg/m 2 (normal weight); 25–29.9 kg/m 2 (overweight) and ≥ 30 kg/m 2 (obese)].…”

Correlation between Age and Body Mass Index (BMI) with Histopathological Features of Breast Cancer Patients in RSUP Haji Adam Malik Medan

“…In general, younger women were more likely to have higher-stage and higher-grade disease [12]. The previous studies have found associations between high BMI and high histologic grade levels [13,14]. The previous study implies that excess body weight contributes to higher tumor stage and grade, including a greater incidence of metastases, specifically in the 80% of breast tumors considered luminal [15].…”

“…In most studies, risk estimates for the relationship between body mass index (BMI) and breast cancer have been adjusted for tumor characteristics (stage at diagnosis and/or tumor size, grade, and nodal status) [15]. Also, obesity is associated with greater size, stage, and grade [13,16]. Numerous studies have documented that young women were more likely to develop more aggressive breast cancer subtypes with unfavorable prognostic features and present with more advanced disease stages [12].…”

Impact of breast cancer risk factors on clinically relevant prognostic biomarkers for primary breast cancer

“…In general, most previous studies examining the relationships between breast cancer risk factors and tumor behavior have focused on the individual tumor characteristics, and not their constellation. Higher BMI, for instance, is reportedly associated with higher grade or larger size tumors; nulliparity and menopausal hormone therapy use (MHT) with highly proliferating and lobular carcinomas, respectively; and higher parity with P53 expressing tumors [ 9 – 12 ]. The impact of these factors on prognostic biomarkers that combine several tumor characteristics to infer tumor aggressiveness and aid treatment recommendation is, however, less well-studied.…”