Abstract

Abstract Background: Pregnancy associated breast cancer (PABC) comprises nearly 4% of all breast cancers. Compared to age-matched non-pregnant breast cancer patients, PABC is generally characterized by a particularly aggressive histopathologic profile. Whether these tumors arise before or during pregnancy, and whether they are stimulated by pregnancy-related hormones and/or epigenetic changes that by itself may affect subsequent hormone concentrations, remains to be elucidated. It is currently even unknown whether the histopathologic profile within PABC patients is affected by gestational age at diagnosis. In addition, some small studies observed a poorer outcome in lactating patients for patients with a postpartum PABC diagnosis. To fill this gap in knowledge, the present study assesses the influence of gestational age and lactation status at diagnosis on the histopathologic profile of PABC in a large population-based cohort.Methods:We identified 741 patients with PABC, between 1988 and 2019, in the nationwide Dutch Pathology Registry (PALGA). Histopathologic features (grade, ER-, PR-, and HER2-receptor status) were compared between pregnant- and postpartum PABC patients. Within pregnant PABC patients, histopathologic features were compared between the three gestational trimesters. For PABC patients with a postpartum diagnosis we compared histopathologic features of lactating versus non-lactating women.Results:Mean age at diagnosis was 34.2 years and the majority of breast cancers were diagnosed during pregnancy (74.2%); of which nearly half during the third trimester (47.3%). Histopathologic features did not differ between pregnant (n=550) and post-partum (n=191) PABC patients. Within pregnant patients, a significantly higher percentage of tumors were ER-receptor negative in the second (56.8%) and third trimester (57.3%), as compared to the first trimester (41.9%) (p=0.0015). A similar pattern was observed for PR; PR-negative receptor-status within first, second and third trimester: 48.0%, 57.7%, 56.5%, though these differences were not statistically significant (p=0.233). For histologic grade, we observed a higher proportion of grade III tumors with the second (87.4%) and third trimester (79.2%), as compared to the first trimester (73.7%) (p=0.055). For postpartum PABC patients no differences were observed for histologic grade between lactating (n=83) and non-lactating patients (n=94). However, tumors of lactating PABC patients were more often ER-negative (62.7% vs 48.9%, p=0.179), PR-negative (66.3% vs. 57.4%, p=0.258) and HER2-negative (74.7% vs. 61.7%, p=0.100). Conclusion:This unique, large population-based study of 741 PABC patients, demonstrates surprising histopathologic differences by gestational age at diagnosis for pregnant PABC-patients, and by lactation status for post-partum PABC-patients, which has not been reported before. Pregnant patients diagnosed at an advanced gestational age and postpartum PABC-patients who are lactating, seem to have a more aggressive histopathologic profile. This renders interesting clues for further studies, that will be conducted to unravel the molecular and genetic background and to investigate whether this has consequences on outcome. Citation Format: Britt BerendineMaria Suelmann, Carmen van Dooijeweert, Carsten Bakhuis, Elsken van der Wall, Sabine Linn, Paul van Diest. The histopathologic profile of pregnancy associated breast cancer by gestational age and lactation: Analysis of the nationwide Dutch Pathology Registry [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 PS7-14.

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