Pregnancy-associated breast cancer: nationwide Dutch study confirms a discriminatory aggressive histopathologic profile

Abstract

Purpose Breast cancer is the most common type of malignancy in pregnant women, occurring approximately once in every 3000 pregnancies. Pregnancy-associated breast cancer (PABC) is commonly defined as breast cancer diagnosed during or within one year after pregnancy, and it accounts for up to 6.9% of all breast cancers in women younger than 45 years old. Whether these cancers arise before or during pregnancy, and whether they are stimulated by the high hormonal environment of pregnancy, is currently unknown. This study assesses the histopathological profile of PABC in a large Dutch population-based cohort. Methods We identified 744 patients with PABC (in this cohort defined as breast cancer diagnosed during or within 6 months after pregnancy) diagnosed between 1988 and 2019, in the nationwide Dutch Pathology Registry (PALGA). An age-matched PALGA cohort of unselected breast cancer patients (≤ 45 years), diagnosed between 2013 and 2016, was used as a control. Histopathologic features of both cohorts were compared. Results The median age of PABC patients was 34.3 years old (range 19–45 years) and most breast cancers were diagnosed during pregnancy (74.2%). As compared to age-matched controls, PABC patients had tumors of higher Bloom–Richardson grade (grade I: 1.5% vs. 12.4%, grade II: 16.9% vs. 31.3%, grade III: 80.3% vs. 39.5%, p < 0.0001). Furthermore, estrogen (ER)- and progesterone (PR)-receptor expression was less frequently reported positive (ER: 38.9% vs. 68.2% and PR: 33.9% vs. 59.0%, p < 0.0001), while a higher percentage of PABC tumors overexpressed HER2 (20.0% vs. 10.0%, p < 0.0001). The most observed intrinsic subtype in PABC was triple-negative breast cancer (38.3% vs. 22.0%, p < 0.0001), whereas hormone-driven cancers were significantly less diagnosed (37.9% vs. 67.3%, p < 0.0001). Conclusion This study, based on a large population-based cohort of 744 PABC Dutch patients, underlines the more aggressive histopathologic profile compared to age-matched breast cancer patients ≤ 45 years. Further in-depth genetic analysis will be performed to unravel the origin of this discriminating phenotype. It definitely calls for timely detection and optimal treatment of this small but delicate subgroup of breast cancer patients.

Genomic copy number alterations as biomarkers for triple negative pregnancy-associated breast cancer

“…In our previous large population based study, triple negative breast cancer (TNBC: ER negative, PR negative, absence of HER-2 overexpression) was the most frequently observed subtype in PABC compared to age-matched non-PABC tumors [27], in line with other case control studies [14,18,28,29].…”

Patología quirúrgica de la mama y su relación con la lactancia

“…El cáncer de mama en el embarazo y lactancia es muy raro, ocurre con una frecuencia de 1 cada 3 000 a 10 000 embarazos, siendo el 1 % a 3 % de todos los cánceres de mama. Se define como carcinoma de mama asociado al embarazo o cáncer gestacional (CG) (23,24). Epidemiología: El CG se define como el cáncer de mama que ocurre durante el embarazo o un año después de este, representa el 6,9 % de todos los tumores en menores de 45 años y 15,6 % en menores de 35 años.…”

Clinical characteristics, pregnancy outcomes and ovarian function of pregnancy-associated breast cancer patients: a retrospective age-matched study

“…For example, patients diagnosed with PABC are younger, suffer a more advanced stage, have larger tumour sizes and have more axillary lymph node metastasis than non-PABC patients [ 3 , 4 ]. The advanced TNM stage at diagnosis of PABC patients might be caused by high levels of oestrogen and progesterone during pregnancy and high levels of prolactin during lactation or delayed diagnosis that was due to physiological changes of the breast during pregnancy or lactation and pathological changes of breast cancer [ 10 , 11 ]. Studies about the most frequent molecular subtype in PABC did not reach a consistent conclusion, most studies about European and American PABC patients showed triple-negative breast cancer (TNBC) was the most frequent one, some studies about Asian PABC patients showed that Luminal B was the most frequent molecular subtype [ 12 – 14 ].…”