Breast Cancer Molecular Subtypes and Receptor-Related Risk Factor Associations: A Cross-Sectional Study

Breast cancer is the most common cancer among women worldwide. This study aimed to determine the frequency of breast cancer molecular subtypes and the associations of ER, PR, and HER2 status with demographic, reproductive, hormonal, and cancer stage in Qazvin, Iran (2021-2023).

In this cross-sectional study, 333 women with primary breast cancer were evaluated. Demographic, reproductive, hormonal, and cancer stage data were extracted from medical records and interviews. ER, PR, HER2, and Ki67 were assessed by immunohistochemistry. Group comparisons were performed using χ ² and t-tests, and multinomial logistic regression was used to determine associations with tumor stage.

The mean age at diagnosis was 50 years. Eighty-two percent of the patients had a history of breastfeeding, and 20.9% reported a family history of breast cancer. The most common molecular subtype was luminal A (47%), followed by luminal B (HER2+: 15%, HER2-: 6%), HER2-enriched (16%), and triple-negative breast cancer (14%). The ER, PR, and HER2 positivity rates were 68.5%, 62.5%, and 32.7%, respectively. ER- and PR- tumors were more frequently diagnosed at advanced stages (stage III: ER- 31.3% vs. ER+ 14.5%; PR- 31.9% vs. PR+ 12.5%). HER2+ tumors were significantly associated with the absence of family history (8.3% vs. 28.2% in HER2-) and higher stage at diagnosis (stage III: 26.0% vs. 16.5%). HER2-positive tumors had significantly higher odds of presenting at stage II (OR = 1.97, p = 0.04) and stage III (OR = 2.35, p = 0.03) compared with stage I, whereas PR-positive tumors were significantly less likely to present at stage III (OR = 0.27, p = 0.03).

Luminal A was the predominant subtype. Hormone receptor and HER2 status correlated with advanced stage, and HER2+ tumors were more frequent in patients without a family history. These results emphasize the importance of molecular profiling.