Do Reproductive Factors Influence T, N, and M Classes of Ductal and Lobular Breast Cancers? A Nation-Wide Follow-Up Study

BACKGROUNDS The clinical tumor-node-metastasis (T, N and M) classes of breast cancers provide important prognostic information. However, the possible association of TNM classes with reproductive factors has remained largely unexplored. Because every woman has a reproductive history, implications to outcome prediction are potentially significant. METHODS During the study period from 2002 through 2008, 5,614 pre- and 27,310 postmenopausal patients were identified in the Swedish Family-Cancer Database. Ordinal logistic regression analysis was used to estimate odds ratios (ORs) for TNM classes of breast cancers by histology. The reproductive variables were parity, age at first and last childbirth and time interval between first and last childbirth. RESULTS Among postmenopausal patients, the ORs for high-T class (T2-T4) (tumor size ≥2 cm) and metastasis were decreased by parity. A late age at first and last childbirth associated with high-T class and the effects were higher for lobular (OR for late age at first childbirth  = 2.85) than ductal carcinoma. Overall, long time interval between first and last childbirth was related to high-T class and metastasis. However, a short time interval between first and last childbirth in patients with late age at first or last childbirth increased the risk of metastasis. Late age at last childbirth was associated with increased occurrence of lobular carcinoma in situ. Among premenopausal ductal carcinoma patients, nulliparity and early age at first childbirth were associated with high-T class. CONCLUSIONS Increasing parity was protective against high-T class and metastasis; late ages at first and last childbirth were risk factors for high-T class in postmenopausal breast cancers. The current decline in parity and delayed age at first childbirth in many countries may negatively influence prognosis of breast cancer.