Multidisciplinary management of pregnancy-related breast cancer and isolated eƯect of pregnancy on maternal prognosis: experience of the Breast Unit of Modena

Title: Multidisciplinary management of pregnancy-related breast cancer and isolated eƯect of pregnancy on maternal prognosis: experience of the Breast Unit of Modena Key words:  Breast cancer  Pregnancy  Breast surgery  Integrated care  Prognosis Background: Pregnancy-related breast cancer (PrBC), defined as breast cancer diagnosed during gestation, is the most common malignancy in pregnancy, with an incidence of 2.4-7.8 per 100,000 births. Although rare, its frequency is increasing due to delayed childbearing. Diagnosis is often challenging, as physiological breast changes can mask symptoms, leading to more advanced disease at presentation. Psychological factors such as anxiety and fear may also contribute to delayed medical consultation. Management requires a trimester-specific and multidisciplinary approach to balance maternal and fetal outcomes. Historically, due to late-stage diagnosis and typically aggressive tumor biology, pregnancy was believed to worsen prognosis. However, growing evidence suggests that, when matched for stage and biology, pregnancy itself does not negatively impact outcomes. Despite these advances, robust data on PrBC remain limited, partly due to its rarity, and partly because it is often grouped with postpartum cases under the broader category of pregnancy-associated breast cancer (PABC), making it diƯicult to obtain precise statistics on the specific characteristics and outcomes of PrBC patients. Aim: The aim of this retrospective monocentric study is to assess whether concurrent pregnancy status influences breast cancer prognosis by comparing PrBC cases with matched non-pregnant controls. Moreover, it will evaluate the impact of multidisciplinary and trimester-specific management on short- and long-term maternal outcomes in PrBC patients treated at the Breast Unit of Modena over the past 15 years. Where available, relevant obstetric data are also considered to contextualize clinical decision- making and maternal care. Methods: Data from 10 pregnant patients diagnosed with PrBC were retrospectively analysed. Clinical, obstetric, and tumor characteristics were reviewed and subjected to descriptive statistical analysis. Where relevant, subgroup analyses were performed. Then, oncologic outcomes (Disease-Free Survival - DFS and Overall Survival - OS) were compared with 100 non-pregnant controls matched by tumor stage, grade, subtype, and histology using basic comparative statistics. No multivariate analysis was performed due to the limited sample size. Results and conclusions: In the 10 pregnant patients analyzed, no recurrences or breast cancer-related deaths occurred during a median follow-up of 5 years. Compared with 100 matched non-pregnant controls, DFS and OS in the PrBC cohort were not inferior. Moreover, in line with data on young patients, PrBC patients presented high rates of triple-negative and grade 3 tumors, along with a notable prevalence of pathogenic or potentially significant genetic mutations. All PrBC patients received guideline-based oncologic treatment, adjusted as necessary for gestational age. Finally, although the results were not statistically significant due to the small sample size, they align with the growing literature suggesting that pregnancy is not an independent negative prognostic factor and, conversely, it is primarily the indirect challenges associated with it that can aƯect clinical outcomes if not managed properly. Timely, multidisciplinary, and personalized care is therefore essential to ensure adequate therapeutic radicality while also safeguarding fetal safety.