A Retrospective Clinical Study of Patients with Pregnancy-Associated Breast Cancer Among Multiple Centers in China (CSBrS-008)
Pregnancy-associated breast cancer (PABC) is a unique and complex form of breast cancer that occurs during pregnancy or within one year after childbirth. This condition poses significant challenges due to its impact on both maternal and fetal health, as well as the complexities involved in its diagnosis and treatment. With the rapid social development and changes in reproductive policies in China, the average age of women at first childbirth is increasing, which is expected to lead to a rise in the incidence of PABC. This study aims to provide a comprehensive understanding of the prevalence, clinicopathological features, treatment strategies, and outcomes of PABC based on a large multicenter sample in China.
The study retrospectively analyzed data from 164 patients diagnosed with PABC across 27 hospitals in China between January 2016 and December 2018. These cases accounted for 0.30% of all breast cancer cases during the same period. Among these patients, 83 were diagnosed during pregnancy, and 81 were diagnosed during lactation. The median age of the patients was 33 years, ranging from 24 to 47 years. The distribution of cancer stages among the patients was as follows: Stage I accounted for 9.1% (15/164), Stage II for 54.9% (90/164), Stage III for 24.4% (40/164), and Stage IV for 2.4% (4/164). In terms of molecular subtypes, 9.1% (15/164) of the patients were luminal A, 43.3% (71/164) were luminal B, 15.2% (25/164) were human epidermal growth factor receptor 2 (Her-2) overexpression, and 18.9% (31/164) were triple-negative breast cancer (TNBC).
For patients diagnosed with PABC during pregnancy, 36.1% (30/83) underwent direct surgery, and 20.5% (17/83) received chemotherapy during pregnancy. Notably, 31.3% (26/83) of these patients chose to terminate their pregnancy through abortion or induction of labor. The median follow-up time for all patients was 36 months, ranging from 3 to 59 months. During this period, 11.0% (18/164) of the patients experienced local recurrence or distant metastasis, and 3.0% (5/164) died. These findings suggest that standardized surgical and chemotherapeutic interventions for PABC are safe and feasible.
The incidence of PABC is relatively low, ranging from 0.2% to 3.8% of all breast cancer cases, but it is particularly significant in women under 30 years old, where it accounts for 10% to 20% of all breast cancers. The increasing average age of first childbirth in China is expected to contribute to a higher incidence of PABC in the future. This study collected data from 27 hospitals through the Chinese Society of Breast Surgery to investigate the prevalence and clinical management of PABC in China.
The clinical data for this study were derived from 60,998 newly diagnosed breast cancer patients treated at 27 hospitals nationwide between January 2016 and December 2018. Among these, 164 patients were pathologically confirmed to have PABC, representing 0.3% of all breast cancer cases during this period. The follow-up deadline was November 31, 2020, with a median follow-up duration of 36 months. Disease-free survival (DFS) was defined as the time from the pathological diagnosis of PABC to relapse or metastasis, while overall survival (OS) was defined as the interval between the pathological diagnosis of PABC and the date of death or the last follow-up.
The clinicopathological characteristics of the 164 patients with PABC revealed that the median age was 33 years, with a range of 24 to 47 years. Among these patients, 15 (8.2%) had a family history of malignancies, and 10 (5.4%) had a family history of breast cancer. The distribution of cancer stages was as follows: Stage 0 (3.7%), Stage I (9.1%), Stage IIa (31.1%), Stage IIb (23.8%), Stage IIIa (16.5%), Stage IIIb (4.9%), Stage IIIc (3.0%), Stage IV (2.4%), and unknown stage (5.5%). In terms of nodal status, 54 cases (33.0%) were N0, 71 cases (43.3%) were N1, 19 cases (11.6%) were N2, and 5 cases (3.0%) were N3. The most common pathological type was invasive ductal carcinoma, accounting for 71.3% (117/164) of cases. The histological grades were distributed as follows: G1 (1.2%), G2 (31.1%), and G3 (30.0%). The molecular subtypes included luminal A (9.1%), luminal B (29.3%), luminal B (Her2+) (14.0%), Her-2-positive breast cancer (15.2%), and TNBC (18.9%).
The outcomes of patients with PABC during pregnancy were analyzed based on the timing of diagnosis. Among the 83 patients diagnosed during pregnancy, 14 were in early pregnancy, 38 in mid-pregnancy, and 31 in late pregnancy. All patients diagnosed in early pregnancy chose to terminate their pregnancy through surgical or medical abortion. In mid-pregnancy, 12 patients opted for medical abortion, while 26 delivered successfully. All patients diagnosed in late pregnancy delivered successfully, with neonates showing normal Apgar scores and healthy development.
The treatment strategies for PABC during pregnancy varied. Among the 83 patients, 30 (36.1%) underwent surgical treatment during pregnancy, including 8 who received breast-conserving surgery and 22 who underwent modified radical mastectomy. Seventeen patients (20.5%) received chemotherapy during pregnancy, including 6 who received neoadjuvant chemotherapy and 11 who received adjuvant chemotherapy. The chemotherapy regimens included weekly paclitaxel and epirubicin plus cyclophosphamide. Among the patients who received chemotherapy during pregnancy, 4 experienced recurrence or metastasis.
The follow-up data revealed that 18 patients (11.0%) experienced local recurrence or distant metastasis, and 5 patients (3.0%) died. The Kaplan-Meier survival curves comparing patients diagnosed during pregnancy and those diagnosed during lactation showed no significant differences in DFS and OS. Similarly, the survival analysis based on Ki-67 index and Her-2 status also showed no significant differences in prognosis.
The study also examined the impact of PABC on neonatal outcomes. Among the 57 patients who continued their pregnancy, 11 were diagnosed in late pregnancy and delivered without any treatment. The remaining 46 patients received chemotherapy or surgery during pregnancy, with 89.1% diagnosed in mid-pregnancy. The neonates delivered by these patients had normal Apgar scores, with 23 neonates weighing more than 2500 grams and 21 neonates weighing less than 2500 grams.
The prognosis of PABC remains a topic of debate. Some studies suggest that the prognosis of PABC is worse than that of non-PABC due to delayed diagnosis and treatment, as well as hormonal stimulation. However, other studies have found no significant difference in prognosis when controlling for factors such as age, tumor stage, and hormone receptor expression. In this study, the median follow-up duration was 36 months, during which 18 patients (11.0%) experienced recurrence or metastasis, and 5 patients (3.0%) died. The survival analysis showed no significant differences in DFS and OS between patients diagnosed during pregnancy and those diagnosed during lactation.
The study also highlighted the importance of early detection and diagnosis of PABC. Breast ultrasound is recommended as the first-choice diagnostic method due to its safety and non-radioactive nature. Mammography with protective measures is also considered safe for the fetus, although its sensitivity may be reduced due to increased breast density during pregnancy.
In conclusion, PABC is a complex and challenging condition that requires careful consideration of both maternal and fetal health. Standardized surgical and chemotherapeutic interventions are safe and feasible for managing PABC during pregnancy. Early detection and diagnosis are crucial for improving outcomes, and further research is needed to better understand the mechanisms underlying PABC and to develop more effective treatment strategies. With the increasing average age of first childbirth in China, the incidence of PABC is expected to rise, highlighting the need for continued research and clinical advancements in this field.
doi.org/10.1097/CM9.0000000000001697
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