The diagnosis of breast cancer during pregnancy represents a challenging situation for the patient, her caregivers and physicians. Pregnancy adds complexity to oncological treatment planning, as many therapies can be potentially dangerous to the fetus. Therefore, a multidisciplinary approach is needed to offer a proper care for obtaining the best possible outcomes for the mother and the future child. Breast surgery is feasible throughout the pregnancy while radiotherapy should be postponed after delivery. Administration of chemotherapy is considered safe and can be given during the second and third trimesters, while it is contraindicated in the first trimester due to the high risk of fetal malformations. Endocrine therapy and targeted agents are not recommended during the whole pregnancy period; however, limited data are available on the use of the majority of new anticancer drugs in this context. The aim of the current review is to provide an update on the current state of art about the management of women diagnosed with breast cancer during pregnancy.

Background: Although use of gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy is an established strategy to protect ovarian function in premenopausal breast cancer patients, no long-term safety data are available, raising some concerns in women with hormone receptor–positive disease. There are controversial data on its fertility preservation potential. Methods: The Prevention of Menopause Induced by Chemotherapy: a Study in Early Breast Cancer Patients—Gruppo Italiano Mammella 6 (PROMISE-GIM6) trial is a multicenter, randomized, open-label, phase III superiority trial conducted at 16 Italian centers from October 2003 to January 2008. Eligible patients were randomly assigned to (neo)adjuvant chemotherapy alone (control arm) or combined with the GnRHa triptorelin (GnRHa arm). The primary planned endpoint was incidence of chemotherapy-induced premature ovarian insufficiency. Post hoc endpoints were disease-free survival (DFS), overall survival (OS), and post-treatment pregnancies. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Results: Of 281 randomly assigned patients, 80.4% had hormone receptor–positive breast cancer. Median follow-up was 12.4 years (interquartile range = 11.3-13.2 years). No differences in 12-year DFS (65.7% [95% CI = 57.0% to 73.1%] in the GnRHa arm vs 69.2% [95% CI = 60.3% to 76.5%] in the control arm; HR = 1.16, 95% CI = 0.76 to 1.77) or in 12-year OS (81.2% [95% CI = 73.6% to 86.8%] in the GnRHa arm vs 81.3% [95% CI = 73.1% to 87.2%] in the control arm; HR = 1.17, 95% CI = 0.67 to 2.03) were observed. In patients with hormone receptor–positive disease, the hazard ratio was 1.02 (95% CI = 0.63 to 1.63) for DFS and 1.12 (95% CI = 0.59 to 2.11) for OS. In the GnRHa and control arms, 9 and 4 patients had a posttreatment pregnancy, respectively (HR = 2.14, 95% CI = 0.66 to 6.92). Conclusions: Final analysis of the PROMISE-GIM6 trial provides reassuring results on the safety of GnRHa use during chemotherapy as a strategy to preserve ovarian function in premenopausal patients with early breast cancer, including those with hormone receptor–positive disease.

Current approaches for cancer detection and characterization are based on radiological procedures coupled with tissue biopsies, despite relevant limitations in terms of overall accuracy and feasibility, including relevant patients’ discomfort. Liquid biopsies enable the minimally invasive collection and analysis of circulating biomarkers released from cancer cells and stroma, representing therefore a promising candidate for the substitution or integration in the current standard of care. Despite the potential, the current clinical applications of liquid biopsies are limited to a few specific purposes. The lack of standardized procedures for the pre-analytical management of body fluids samples and the detection of circulating biomarkers is one of the main factors impacting the effective advancement in the applicability of liquid biopsies to clinical practice. The aim of this work, besides depicting current methods for samples collection, storage, quality check and biomarker extraction, is to review the current techniques aimed at analyzing one of the main circulating biomarkers assessed through liquid biopsy, namely cell-free nucleic acids, with particular regard to circulating tumor DNA (ctDNA). ctDNA current and potential applications are reviewed as well.

Objective: Atypical ductal hyperplasia (ADH) is a proliferative lesion associated with a variable increased risk of breast malignancy, but the management of the patients is still not completely defined, with mandatory surgical excision in most cases. To report the results of the conservative management with mammographic checks of patients with ADH diagnosed by vacuum assisted breast biopsy (VAB), without residual calcifications. Methods: The authors accessed the institutional database of radiological, surgical and pathological anatomy. Inclusion criteria were: ADH diagnosed by VAB on a single group of microcalcifications, without residual post-procedure; follow-up at least of 12 months. Exclusion criteria were the presence of personal history of breast cancer or other high-risk lesions; association with other synchronous lesions, both more and less advanced proliferative lesions. Results: The 65 included patients were all females, with age range of 40–79 years (mean 54 years). The maximum diameter range of the groups of microcalcifications was 4–11 mm (mean 6.2 mm), all classified as BI-RADS 4b (Breast Imaging Reporting and Data System 4b) and defined as fine pleomorphic in 29 cases (45%) or amorphous in 36 cases (55%). The range of follow-up length was 12–156 months (mean 67 months). Only one patients developed new microcalcifications, in the same breast, 48 months after and 15 mm from the first VAB, interpreted as low-grade ductal carcinoma in situ (DCIS) at surgical excision. Conclusion: These results could justify the conservative management, in a selected group of patients, being the malignancy rate lower than 2%, considered in the literature as the “probably benign” definition. Advances in knowledge: Increasing the length of follow-up of selected patients conservatively managed can improve the management of ADH cases.