This clinical perspective evaluates the implications of recent registry-based findings that associate desogestrel-containing hormonal contraceptives with early-onset breast cancer, considering potential modifications to clinical practice. The analysis focused on cancers diagnosed before age 50 that are significantly shaped by the epidemiology of early-onset breast cancer, the transient postpartum increased risk of breast cancer, genetic susceptibility, and the clinical selection of progestin-only methods for women with cardiometabolic risk. Associations observed with desogestrel may reflect residual confounding from postpartum timing, breastfeeding duration, and metabolic factors, rather than drug-specific carcinogenicity. Due to the many drawbacks of the registry study, the current evidence does not support discouraging the use of desogestrel during lactation or in patients contraindicated for oestrogen, de facto depriving many women of the possibility to perform an appropriate hormonal contraception. This paper delineates methodological priorities for future research to effectively distinguish biological effects from reproductive and metabolic confounding factors.

Background/Objectives: This study aims to assess the effects of combined hormonal contraceptives (CHCs) on bone metabolism markers. It primarily measures osteocalcin and additionally examines other bone health markers, seeking to determine their responses to estrogen–progestogen treatments. Methods: This study involved a comprehensive evaluation of the pertinent literature and a meta-analysis explicitly conducted on data describing women of reproductive age. The analysis encompassed accessible papers ranging to December 2024 (i.e., those listed in PubMed/Medline, Embase, Scopus, the Cochrane Database, International Clinical Trials Registry, and ClinicalTrials.gov). We examined published randomized controlled trials (RCTs) and prospective studies. The quality of the studies was assessed using the Cochrane tool for RCTs and the Newcastle–Ottawa Scale for prospective studies. The selected indicators for primary and secondary outcomes were ascertained by standardized mean change (SMC), displaying the difference between conditions before and after treatment. Trends were evaluated using meta-regressions. Results: Ultimately, 34 articles out of 1924 identified items met the inclusion criteria, covering 33 unique studies. In EE/E4 combinations, osteocalcin dropped significantly (SMC −0.54 (CI.95 −0.64/−0.43) and −0.43 (CI.95 −0.76/−0.10)). Similar effects were observed for other bone-formation and reabsorption markers, with less significant reductions observed in E2-containing CHC (e.g., alkaline phosphatase (bone) EE combinations, SMC −0.39 (CI.95 −0.67/−0.11); P1NP E2 combination, 0.12 (CI.95 −0.10/0.33); and EE combinations, −0.55 (CI.95 −0.83/−0.26)). The reduction patterns also exhibited differences according to the women’s age (e.g., osteocalcin in EE combinations ≤21, SMC −0.63 (CI.95 −0.77/−0.49) and >21, SMC −0.42 (CI.95 −0.61/−0.24); alkaline phosphatase (bone) EE combinations ≤21, SMC −0.55 (CI.95 −0.86/−0.24) and >21, SMC −0.06 (CI.95 −0.47/0.35)). This analysis found that CHC maintains or reduces bone turnover in childbearing women, with effects varying by age and hormone combination. Moreover, bone-formation and reabsorption markers correlated positively to pro-androgenic progestins (p < 0.05). Thus, estrogen–progestogen combinations reduce bone turnover less when weak estrogens and a pro-androgenic or neutral progestin are present. Conclusions: This study found that CHCs reduce bone turnover, with natural estrogens and androgenic progestins appearing to be more beneficial than EE and anti-androgenic types. These findings would potentially influence decisions relevant to CHC prescriptions during a woman’s reproductive phases, emphasizing the need for additional research to tailor CHC usage to bone health.

PURPOSE:The purpose of this phase 2 clinical study is to investigate the safety and feasibility of a single fraction stereotactic partial breast irradiation (S-PBI) for early-stage breast cancer in the preoperative setting and to evaluate tumor response to a single large radiation dose through pathologic examination and immunohistochemistry analysis of the surgical specimen. METHODS AND MATERIALS:This single arm, phase 2 clinical trial includes patients in postmenopausal status, over the age of 50 years, with early-stage (cT1-T2 cN0) breast cancer, luminal type, any grade, unifocal tumor, and suitable for breast conserving surgery. The gross tumor volume includes the tumor. The clinical target volume corresponds to gross tumor volume. The planning target volume is created by adding 3 mm symmetrical margins from the clinical target volume. Treatment is delivered through GammaPod technology as single fraction radiosurgery, to a total dose of 30 to 36 Gy. Surgery is performed 8 to 28 weeks after S-PBI. Pathologic response is classified as pathologic complete response (pCR), near complete response with <10% of residual disease, pathologic partial response with 10% to 90% of residual disease, or stable disease with >90% of residual disease. We further group pCR and near complete response together as "Major Response." RESULTS:From January 2022 to November 2023, 49 patients were enrolled and underwent S-PBI followed by breast conserving surgery. The rate of Major Response was 37%, including pCR in 18% of cases. The mean Ki-67 index was reduced from 9.5% pre-S-PBI to 2% post-S-PBI. CONCLUSIONS:Preoperative single fraction S-PBI appears to be associated with a promising rate of "Major Response," including cases of complete response.

Purpose:This study aims to investigate whether there are subgroups of patients with early-stage breast cancer (BC) treated with radical mastectomy that are at high risk of locoregional recurrence (LRR) and could benefit from postmastectomy radiation therapy (PMRT). Methods and Materials:We retrospectively reviewed patients with early-stage BC treated with mastectomy at our institution between December 2009 and December 2018. Tumors were classified according to molecular subtype and known prognostic factors. Outcomes were estimated using the Kaplan-Meier method. Univariate analysis was performed using the log-rank test, while Cox proportional hazards regression was applied to estimate hazard ratios for evaluating associations between prognostic factors and survival. A P value of <.05 was considered statistically significant. Results:A total of 670 patients who met the selection criteria were identified. Median age was 59.4 years (IQR, 48-72), and the median follow-up was 107.1 months (IQR, 80.3-138.6). Among the cohort, 257 patients (38.3%) had T2 tumors, 249 (37.1%) were pN1, 186 (27.8%) had grade 3 tumors, 134 (20%) presented with lymphovascular invasion (LVI), 116 (17.3%) were HER2-positive, and 55 (8.2%) had triple-negative disease. LRR rates at 2, 5, and 8 years were 1.4%, 2.9%, and 3.5%, respectively. On univariate analysis, the presence of LVI, G3, tumor size (T), nodal involvement (pN1), estrogen receptor-negative status, triple-negative phenotype, and Ki-67 expression were significantly associated with an increased risk of LRR. Notably, LVI-positive patients had significantly higher locoregional and regional recurrence rates at 8 years (9.5% and 9.4%, respectively) compared to LVI-negative patients (1% and 1.1%). Multivariate analysis confirmed LVI as a strong and independent predictor of recurrence across all models. Conclusions:This study confirms the prognostic relevance of several pathologic factors in predicting LRR, with particular emphasis on the independent role of LVI, in patients with early-stage BC treated with mastectomy and not receiving PMRT. In patients with early-stage BC with T1-T2 tumors and 1-3 positive axillary lymph nodes with the presence of LVI, PMRT should be considered.

Breast cancer is a significant health issue for women worldwide and poses unique challenges for all ages. Older women face many concerns about breast cancer treatment and outcomes. This study aims to compare breast cancer management and outcomes across various age groups within a single-center experience in a region with an aging population, focusing specifically on women aged 70 and older to identify potential disparities in treatment and prognosis. We conducted a retrospective analysis of all female patients diagnosed with breast cancer at our local reference Breast Unit in northeastern Italy between January 2002 and July 2023. The primary outcome measures in this study were overall survival (OS), disease-free survival (DFS), cumulative loco-regional recurrences, and cumulative distant recurrences. The study included 2478 women over 70 (31.12

ABSTRACT Objective This study aimed to identify risk factors associated with the development of metastases in breast cancer patients, to investigate survival rates, and the relationship between local recurrences and distant metastases. Methods This retrospective case‐cohort study included women with breast cancer who were treated at a certified Breast Unit between 2001 and 2015. Cases who developed distant metastases were compared to controls based on diagnosis year, stage, and age at diagnosis. Comprehensive information on patient characteristics, tumor biology, and treatment options was gathered. Results The study included 412 patients who developed distant metastases and 433 controls who remained metastasis‐free over a median follow‐up of 150 months (interquartile range 87–202). The 20‐year overall survival was 99.23% for the control group and 23.62% for those with metastasis (p < 0.01). Significant risk factors for metastasis included lobular invasive carcinoma (odds ratio (OR) 2.26, p < 0.001), triple‐negative subtype (OR 4.06, p = 0.002), high tumor grade (OR 2.62, p = 0.004), larger tumor size (OR 1.02, p < 0.001), lymph node involvement (p < 0.001), and loco‐regional recurrence (OR 4.32, p < 0.001). Progesterone receptor (PR) expression was protective (OR 0.52, 95% confidence interval 0.34–0.81, p = 0.003). Machine learning models supported these findings, though their clinical significance was limited. Conclusions Lobular invasive carcinoma, specific tumor subtypes, high grade, large tumor size, lymph node involvement, and loco‐regional recurrence are all significant risk factors for distant metastasis, whereas PR expression is protective. The potential of machine learning in predicting metastasis was explored, showing promise for future personalized risk assessment.

Purpose/Objective(s) To assess the value of breast MRI and contrast-enhanced mammography (CEM) to identify pathologic major response in patients with early-stage breast cancer undergoing pre-operative S-PBI. Materials/Methods We conducted a phase II clinical trial enrolling women older than 50, with proven breast invasive non special type carcinoma, hormonal receptors positive/HER2 negative, any grade, tumor size < 3cm, unifocal, without nodal involvement, and candidates to conservative surgery. The Gross Tumor Volume (GTV) comprised the tumor. The Clinical Target Volume (CTV) was equal to GTV. The Planning Target Volume (PTV) was created by adding a 3 mm margin to CTV. The total dose was 30-36 Gy prescribed to the 95% of the PTV. Patients had a breast MRI or CEM 3 months after S-PBI and underwent surgery at 4 months. The radiological response was described as no evidence of disease (rNED) or partial response (rPR) if any residual tumor was detectable. Pathologic response was classified as complete (pCR, absence of residual tumor), near pCR (npCR, <10% invasive tumor left), partial (pPR, <50% tumor left), or stable disease (pSD, no response). Pathologic “major response” included patients with pCR and npCR. Radiology-pathology correlation was conducted and post- S-PBI positive (PPV) and negative predictive (NPV) value calculated. Results From January 2022 to January 2024, 52 women had S-PBI followed by conservative breast surgery. The analysis was conducting on 46 patients who underwent post-S-PBI breast MRI (n = 41) or CEM (n = 5). The rNED on imaging was reported in 29/46 (63%) cases, while major pathologic response was documented in 15/46 (33%) cases. Among the 29 patients with rNED, there were 14 cases with pCR+npCR, for a NPV of 48%. Among the 17 cases with rPR on imaging, there were 16 cases with residual tumor at pathology (pPR+pSD) for a PPV of 94%. Conclusion Post S-PBI breast MRI and CEM have high PPV (94%) for detection of residual tumor, although limited NPV (48%) for the detection of major pathologic response. Our results do not support the use of negative pre-operative imaging to avoid breast surgery.

Objective The Moon has a noticeable influence on the Earth due to its gravity, the most visible manifestation of which are tides. We aimed to see if the Moon's daily cycle, like the Sun's, affects the prevalence and incidence of childbirth. Methods In this retrospective cohort study, we examined all deliveries at the Academic Hospital of Udine between 2001 and 2019. All consecutive singleton pregnancies with spontaneous labor and vaginal delivery were included. Results During the period, 13,349 singleton pregnancies with spontaneous labor and vaginal delivery were delivered in 6939 days. A significantly higher prevalence of deliveries was found with the Moon above the horizon (50.63% vs. 49.37%, p < 0.05). Moreover, during the day, there was a significantly higher prevalence of deliveries than during nighttime (53.74% vs. 45.79%, p < 0.05). Combining the Moon and Sun altitude, the majority of deliveries were registered when both were above the horizon (27.39% vs. 26.13%, 23.25%, or 23.24%, p < 0.05). These findings were confirmed in multivariate analysis after adjusting for parity, gestational age, or season. We found no correlation between birth and the Moon phase. Conclusions Our data support the interaction of the Moon and the Sun in determining the time of birth. More research is needed to understand these phenomena and improve our understanding of labor initiation mechanisms.

Abstract Background Pregnancy-related cancers are mostly breast cancers, and their incidence is likely to increase as a result of the modern trend of delaying childbearing. In particular, advanced maternal age increases breast cancer risk, and younger breast cancer patients are more likely to die and metastasize. This study compared a population with a high incidence of delayed childbearing with another population with a lower mean age at childbirth in order to determine whether breast cancer diagnosis and childbearing age overlap. Methods We retrospectively analyzed multiple data sources. The Surveillance, Epidemiology, and End Results (SEER) program, the United States National Center for Health Statistics as part of the National Vital Statistics System, the United Nations Population Division, the GLOBOCAN Cancer Observatory, the CLIO-INFRA project database, the Human Fertility Database, and anonymized local data were used. Results As women’s age at delivery increased, the convergence between their age distribution at breast cancer diagnosis and childbearing increased. In addition, the overlap between the two age distributions increased by more than 200% as the average age at delivery increased from 27 to 35 years. Conclusions As women’s average childbearing age has progressively risen, pregnancy and breast cancer age distributions have significantly overlapped. This finding emphasizes the need for increased awareness and educational efforts to inform women about the potential consequences of delayed childbearing. By providing comprehensive information and support, women can make more informed decisions about their reproductive health and cancer prevention strategies.

Single-fraction pre-operative stereotactic radiosurgery for early-stage breast cancer leads to a high rate of complete or partial pathological response with surgery performed at 2-4 months following irradiation.

This narrative review aims to clarify the role of breast and gynecological risk-reduction surgery in BRCA mutation carriers. We examine the indications, contraindications, complications, technical aspects, timing, economic impact, ethical issues, and prognostic benefits of the most common prophylactic surgical options from the perspectives of a breast surgeon and a gynecologist. A comprehensive literature review was conducted using the PubMed/Medline, Scopus, and EMBASE databases. The databases were explored from their inceptions to August 2022. Three independent reviewers screened the items and selected those most relevant to this review's scope. BRCA1/2 mutation carriers are significantly more likely to develop breast, ovarian, and serous endometrial cancer. Because of the Angelina effect, there has been a significant increase in bilateral risk-reducing mastectomy (BRRM) since 2013. BRRM and risk-reducing salpingo-oophorectomy (RRSO) significantly reduce the risk of developing breast and ovarian cancer. RRSO has significant side effects, including an impact on fertility and early menopause (i.e., vasomotor symptoms, cardiovascular disease, osteoporosis, cognitive impairment, and sexual dysfunction). Hormonal therapy can help with these symptoms. Because of the lower risk of developing breast cancer in the residual mammary gland tissue after BRRM, estrogen-only treatments have an advantage over an estrogen/progesterone combined treatment. Risk-reducing hysterectomy allows for estrogen-only treatments and lowers the risk of endometrial cancer. Although prophylactic surgery reduces the cancer risk, it has disadvantages associated with early menopause. A multidisciplinary team must carefully inform the woman who chooses this path of the broad spectrum of implications, from cancer risk reduction to hormonal therapies.

Millions of women give birth every year worldwide [...]

Background: The introduction of skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) with immediate reconstruction allowed a noticeable improvement in reconstructive surgery aesthetic results and patients' psychophysical well-being. In any case, there are still concerns about the long-term oncological safety of these two procedures. This study aims to assess the oncological outcomes of women who underwent SSM and NSM and to compare them with traditional modified total mastectomy (MTM). The secondary outcome was to compare mastectomy with breast-conserving surgery (BCS) outcome. Methods: We performed a retrospective chart review study concerning all patients who had experienced SSM and NSM in our Clinic between January 2004 and July 2013. The main outcomes were overall survival (OS), disease-free survival (DFS), and recurrences cumulative rate. Results: Among this study's 1836 invasive breast carcinomas, we found NSM (86.7, 95% confidence interval (CI), 76.7-98.0%) to have a significantly shorter 5-year DFS than MTM (90.4%, 95% CI, 87.9-93.0%). Furthermore, low body mass index (odds ratio (OR) 0.733, p = 0.056), basal-like molecular subtype (OR 28.932, p < 0.05), extended intraductal component (OR 11.160, p = 0.107), and lymph node metastasis extracapsular invasion (OR 8.727, p = 0.077) were the most significant predictors of recurrence in women treated with NSM. Furthermore, patients with BCS had significantly longer OS and DFS than those who underwent MTM. Conclusions: Occult nipple neoplastic involvement following negative intraoperative histological examination of subareolar tissue may explain the higher recurrence rate among women undergoing NSM. Patients with one or more risk factors for recurrence after NSM, such as basal-like molecular subtype, extended intraductal component, and extracapsular invasion of lymph node metastasis, should be given special attention.