We reviewed 25 studies conducted over the past 20 years to gain a deeper understanding of PABC (Table 2). The incidence of PABC reportedly ranges from 0.2-3.8% [3,4,6]. PABC used to be a rare disease in China. However, recently, the number of cases increased. In our study, we observed that the frequency of PABC in non-first pregnancy women has increased as women started to have second children since Chinese authority abolished the restriction that couples could only have one child. Our study found that the proportion of PABC developed in non-first pregnancy women was 5.7-fold higher than that developed in first-pregnancy women. We reviewed the literature and found a study conducted in Taiwan that enrolled 26 PABC patients, and most patients (n=18) were first-pregnancy women . These inconsistent results may be due to the small enrollment number. As the largest breast center in East China, our center has treated more than 6,000 primary breast cancer patients per year, ensuring less bias in our study. Other than the above-mentioned study, we found no other studies mentioning the difference in the incidence of PABC between first-pregnancy women and non-first pregnancy women.
In our study, we observed a significant difference in the molecular subtypes between the PABC and non-PABC cases. Luminal B breast cancer accounted for the largest proportion of all PABC patients, followed by triple-negative breast cancer. Consistent with our study, Soo reported that luminal B breast cancer (43.6%) and TNBC (35.9%) predominated in PABC ; while one study presented a different conclusion and showed that TNBC ranked first (48.4%) . Some studies did not list the molecular types but reported the HR and HER-2 status and demonstrated that PABC was more prone to be HR-negative tumors, but no difference in the HER-2 status was reported compared with non-PABC as follows: HR negative (50.0% in PABC vs. 36.1% in non-PABC, P<0.001 (Yun et al.)) , HR negative (32.6% in PABC vs. 15.9% in non-PABC, P=0.014 (Jessica et al.)) , and HR negative (59.4% in PABC vs. 34.4% in non-PABC, P=0.03 (Michael et al.)) ; only one study reported by Soo showed a higher HER-2 positive rate in PABC patients as follows: HER-2 positive (38.5% in PABC vs. 19.2% in non-PABC, P=0.006) . Although these views vary, all studies indicated that PABC tended to present with more aggressive tumors.
The 3-year disease free survival (DFS) of all PABC patients at FUSCC was 80.3%. We reviewed the literature, and the survival of PABC patients reportedly fluctuates over a large range. Wagner reported a very low survival as follows: 5-year overall survival (OS) of 29.7% and 10-year OS of 19.2% among PABC patients ; however, Carole showed that the 5-year OS was 87.5% and that the 10-year OS was 70.0% . The survival rates of the PABC patients compared to those of the non-PABC patients were conflicting. Most studies [8,9,15,10,14,16-22] demonstrated a worse prognosis in PABC after excluding prognostic factors, including age, the tumor size, and lymph node status, while eight studies [23-30] showed no difference in survival between PABC and non-PABC patients after correcting for these factors.
Our analysis showed that the Kaplan-Meier survival curve of the first-pregnancy group was below that of the non-first-pregnancy group. However, there was no statistically significant difference. We speculate that the two groups might have survival differences, but these differences are unclear in this study due to the rare incidence and limited case number. We have no supporter. We will collect more cases to make it clear in ten years.
Five studies classified PABC into antepartum and postpartum breast cancer, and three studies showed that the prognosis of PABC occurring postpartum was worse than that of PABC occurring during gestation [7,12,31]; Mathelin concluded that the prognosis of PABC occurring during the antepartum period was worse ; and Daling indicated that PABC occurring postpartum had a worse survival rate than non-PABC . The survival analysis in our study showed no difference. In our study, we found that patients in early pregnancy were more likely to terminate their pregnancies, while those in late pregnancy usually preferred to delay treatment until the delivery of the fetus.
Starting chemotherapy in mid-late pregnancy without delaying chemotherapy until after delivery is generally preferred as unnecessary delays may result in a worse prognosis. FAC (fluorouracil, adriamycin and cyclophosphamide) is a commonly used chemotherapy regimen that has been shown to be safe in mid-late pregnancy . Doxorubicin and cyclophosphamide can be excreted through milk and, therefore, are prohibited during lactation . However, in China, people generally do not undergo chemotherapy during mid-late pregnancy. Mid-pregnancy women with PABC choose to either terminate the pregnancy or delay chemotherapy until delivery, while late-pregnancy women usually start chemotherapy treatment after delivery. In our study population, 20 (30.3%) PABC patients with HER-2 positivity did not receive Herceptin treatment, including 18 (85.7%) patients who were diagnosed with PABC before 2017. In China, Herceptin was not included in the scope of medical insurance reimbursement until 2017.
It should be acknowledged that there were some limitations in our present study. This study was a single-center study. The follow-up of the patients in the non-first-pregnancy group was short because the restriction was abolished in 2015. We could only obtain the 3-year DFS data. Moreover, some tumor characteristics were absent. The HER-2 status of 9 people was unknown probably because the patients refused to undergo further FISH analyses due to the high cost at that time.