Breast Cancer Risk and Prevention: A Step Forward.

Breast cancer (BC) is a leading topic in medical research as it is the most common cancer occurring in women worldwide; its incidence is progressively increasing in all age groups [...].

Breast Lesions of Uncertain Malignant Potential (B3) and the Risk of Breast Cancer Development: A Long-Term Follow-Up Study.

Breast lesions of uncertain malignant potential (B3) are frequently diagnosed in the era of breast cancer (BC) screening and their management is controversial. They are generally removed surgically, but some international organizations and guidelines for breast research suggest follow-up care alone or, more recently, propose vacuum-assisted excision (VAE). The risk of upgrade to BC is known, but very little data exist on its role as risk factor for future BC development. We analyzed 966 B3 lesions diagnosed at our institution, 731 of which had long-term follow-up available. Surgical removal was performed in 91%, VAE in 3.8%, and follow-up in 5.2% of cases. The B3 lesions included flat epithelial atypia (FEA), atypical ductal hyperplasia (ADH), lobular intraepithelial neoplasia (LIN), atypical papillary lesions (PLs), radial scars (RSs), and others. Overall, immediate upgrade to BC (invasive or in situ) was 22.7%. After long-term follow-up, 9.2% of the patients were diagnosed with BC in the same or contralateral breast. The highest risk was associated with ADH diagnosis, with 39.8% of patients upgraded and 13.6% with a future BC diagnosis (p < 0.0001). These data support the idea that B3 lesions should be removed and provide evidence to suggest annual screening mammography for women after a B3 diagnosis because their BC risk is considerably increased.

Reducing the Use of Frozen Section for Sentinel Node Biopsy in Breast Carcinoma: Feasibility and Outcome.

BACKGROUND/AIM: Sentinel lymph node biopsy (SLNB) is a standard practice for staging the axilla in breast cancer. Initially, intraoperative frozen section (FS) examination was used but was time-consuming and often provided false-negative results. Delayed permanent section (PS) analysis is currently performed; FS-SLNB is maintained for selected high-risk cases. The aim of this study was to evaluate the feasibility of this approach. PATIENTS AND METHODS: All patients with breast cancer with clinically negative lymph nodes undergoing SLNB at our institution from 2004 to 2020 were analyzed, comparing operative time, re-operation rate and clinical outcome in terms of regional lymphatic recurrence-free and overall survival by type of SLNB (FS vs. PS). RESULTS: FS-SLNB comprised 100% of the procedures in 2004 and 18.2% at the end of the study period. The use of PS-SLNB instead of FS-SLNB was associated with a significantly reduced rate of axillary dissection (AD): 4.4% vs. 27.2, respectively (p<0.001). There was no significant difference in re-operation rate for AD: 3.9% vs. 6.9%, respectively (p=0.20). The use of PS-SLNB significantly reduced the operative time (mean=51 minutes) (p<0.001). After a mean follow-up of 70.9 months (range=16-180 months) there were no differences in regional lymphatic recurrence free or overall survival. CONCLUSION: The reduced use of FS-SLNB resulted in a significantly lower rate of AD, and significant operative time and costs savings, without any increase in the reoperation rate and lymphatic recurrences. Therefore, this approach is feasible, safe and beneficial, both for patients and healthcare services.

Breast cancer in pregnancy: concurrent cesarean section, nipple-sparing mastectomy, and immediate breast reconstruction-case report.

Background: Pregnancy-associated breast cancer (PABC), with an incidence rate from 1:3,000 to 1:10,000 deliveries, is the most frequent cancer during pregnancy. PABC appropriate management must take into consideration both the maternal oncological safety and the fetal health, thus posing a challenge for the mother, the baby, and the clinicians. The treatment should adhere as closely as possible to the breast cancer (BC) guidelines. Therefore, surgery is a mainstay, and, when mastectomy is required, breast reconstruction (BR) is a topic of debate. To minimize the risks to the baby, most surgeons postpone BR to delivery. However, a delayed breast reconstruction (DBR) could affect the outcome. In the present case, we report cesarean section concurrent with mastectomy and immediate breast reconstruction (IBR). Methods: A 37-year-old patient, at the 36th week of pregnancy with PABC, underwent simultaneous cesarean delivery, nipple-sparing mastectomy, and IBR. To minimize risks for the newborn, cesarean was firstly performed under spinal anesthesia. Immediately after, breast surgery, including mastectomy and IBR, was performed under general anesthesia. Partial submuscular IBR with an acellular porcine dermal matrix concluded the surgical procedure. Lactation was inhibited, and adjuvant chemotherapy and hormone therapy were administered to the patient. Results: In a single surgical session, cesarean delivery, subcutaneous mastectomy, axillary dissection, and IBR were successfully carried out. No early or late postoperative complications were reported for both the patient and the newborn. Histopathological investigation reported a multifocal and multicentric infiltrating ductal carcinoma. After a 6-year follow-up, the patient is alive and well. Conclusion: To the best of our knowledge, this is the first reported case of concomitant cesarean delivery, PABC mastectomy, axillary dissection, and IBR. This surgical strategy allowed PABC treatment by the BC guideline, minimizing the newborn's disadvantage and permitting, at the same time, the best final BR outcome.

Promote Community Engagement in Participatory Research for Improving Breast Cancer Prevention: The P.I.N.K. Study Framework.

Breast cancer (BC) has overtaken lung cancer as the most common cancer in the world and the projected incidence rates show a further increase. Early detection through population screening remains the cornerstone of BC control, but a progressive change from early diagnosis only-based to a personalized preventive and risk-reducing approach is widely debated. Risk-stratification models, which also include personal lifestyle risk factors, are under evaluation, although the documentation burden to gather population-based data is relevant and traditional data collection methods show some limitations. This paper provides the preliminary results from the analysis of clinical data provided by radiologists and lifestyle data collected using self-administered questionnaires from 5601 post-menopausal women. The weight of the combinations of women's personal features and lifestyle habits on the BC risk were estimated by combining a model-driven and a data-driven approach to analysis. The weight of each factor on cancer occurrence was assessed using a logistic model. Additionally, communities of women sharing common features were identified and combined in risk profiles using social network analysis techniques. Our results suggest that preventive programs focused on increasing physical activity should be widely promoted, in particular among the oldest women. Additionally, current findings suggest that pregnancy, breast-feeding, salt limitation, and oral contraception use could have different effects on cancer risk, based on the overall woman's risk profile. To overcome the limitations of our data, this work also introduces a mobile health tool, the Dress-PINK, designed to collect real patients' data in an innovative way for improving women's response rate, data accuracy, and completeness as well as the timeliness of data availability. Finally, the tool provides tailored prevention messages to promote critical consciousness, critical thinking, and increased health literacy among the general population.

Nuclear Expression of ß-Catenin Is Associated with Improved Outcomes in Endometrial Cancer.

Beta-catenin is involved in intercellular adhesion and participates in the Wnt signaling pathway. This study evaluated the expression pattern and prognostic value of ß-catenin in a series of endometrial carcinoma patients. Immunohistochemical analyses were used to assess the expression and subcellular localization of ß-catenin from tissue sections of 74 patients with endometrial carcinoma. No correlation was found between beta-catenin expression and clinicopathological parameters. Patients expressing nuclear ß-catenin (n = 13; 16%) showed a more favorable prognosis than patients expressing membranous ß-catenin; the 5-year disease-related survival rate was 100% for cases expressing nuclear ß-catenin, compared with 73.8% (SE 0.08) of cases expressing membranous ß-catenin (p = 0.04). Although statistical significance was not reached (p = 0.15), cases expressing nuclear ß-catenin showed a 5-year disease-free survival rate of 90.9% (SE 0.08) compared with 67.4% (SE 0.08) of cases expressing membranous ß-catenin. Univariate Cox analysis revealed that membranous ß-catenin expression was found to be associated with a relative risk of death of 33.9 (p = 0.04). The stage of disease (p = 0.0006), histology (p = 0.003), and grading (p = 0.008) were also significantly correlated with disease-free survival according to univariate Cox analyses. Determining ß-catenin expression and localization patterns may predict survival in patients with endometrial cancer and, therefore, should be considered a potential prognostic marker of disease.

Prognostic Factors Research in Breast Cancer Patients: New Paths.

Breast cancer is the most frequent tumor among women worldwide [...].

Intertwining art, religion and anatomy: did Michelangelo Buonarroti influence Berengario da Carpi's representation of a maternal death?

AIM: To confirm that the sixteenth century surgeon-anatomist, Jacopo Berengario da Carpi, used a woman who died of a ruptured uterus as a model for a woodcut of female genital anatomy, and that the presentation was based on the cloak in Michelangelo's Creation of Adam after visiting the Sistine Chapel in the Vatican whilst he was in Rome. METHOD: Analysis of the woodcut for evidence of a uterus at term, and comparison with the shape of the cloak in the Creation of Adam, coupled with Berengario's own description. RESULTS: The size of the uterus is that in the 38th to 40th week of pregnancy, further supported by striations of the endometrial surface, rather than the smooth surface of the non-gravid. By rotating the woman's image 90° counterclockwise, the outline of the woman's cloak becomes almost perfectly superimposed over God's cloak. CONCLUSION: In the woodcut, the open belly of the model shows typical features of the full-term uterus. The use of God's cloak softens the features. At the same time, it exemplifies the creative power of God and describes the birth of humanity in both theological and physiological ways. Intertwining art, religion and anatomy, Michelangelo and Berengario allow scholars to appreciate the concepts of divinity and humanity at multiple levels.

Immunohistochemical Evaluation of FGD3 Expression: A New Strong Prognostic Factor in Invasive Breast Cancer.

Among new prognostic factors for breast cancer, the most promising one seems to be FGD3 (Facio-Genital Dysplasia 3) gene, whose expression improves outcome by inhibiting cell migration. The aim of the study was to evaluate the prognostic role of FGD3 in invasive breast cancer in a series of 401 women, treated at our unit, by evaluating the expression of this gene by immunohistochemistry. Patients with high FGD3 expression showed a significantly better disease-free survival (DFS) (p < 0.001) and overall survival (OS) (p < 0.001). The prognostic value of FGD3 expression was stronger than that of classical pathologic parameters such as histological grade of differentiation, Ki-67 index and molecular subtype. By multivariate Cox analysis, FGD3 expression was confirmed as significant and independent prognostic factor, ranking second after age at diagnosis (≤40 years) for DFS (p = 0.003) and the second strongest predictor of OS, after AJCC Stage (p < 0.001). Our data suggest that inclusion of FGD3 evaluation in the routine workup of breast cancer patients may result in a more accurate stratification of the individual risk. The possibility to assess FGD3 expression by a simple and cheap technique such as immunohistochemistry may enhance the spread of its use in the clinical practice.

Immediate-implant-based-breast-reconstruction with two-stage expander-implant reconstruction versus one-stage-reconstruction with acellular dermal matrix: analysis of patients' satisfaction.

Background The aim of this retrospective study is to evaluate the patient-reported outcome after immediate ADM-assisted implant- based breast reconstruction. Material and Methods Patients underwent breast reconstruction from 2015 to 2019 have been retrospectively divided into group A (partial subpectoral implant and ADM and group B (expander/implant). For each patient we evaluated retrospectively postoperative complications and patients' satisfaction. Results 26 patients from the case group and 40 from the control group completed the BREAST-Q. The incidence of complications in the cases was 18.4%, while in the control group was 20.4%.  We found no statistical difference in most of the domains and in the mean score of the questionnaire (mean score cases=69.0±14.4 vs controls=68.4±15.7; p=0.888). A significant difference results only in the domains Q2a and Q2b, sensation of rippling. Conclusions. The use of ADM in one-stage reconstruction allows to perform breast reconstruction in only one surgery, with similar complication rates and patient satisfaction.

Establishment and characterization of a new spontaneously immortalized ER-/PR-/HER2+ human breast cancer cell line, DHSF-BR16.

Invasive ductal carcinoma (IDC) constitutes the most frequent malignant cancer endangering women's health. In this study, a new spontaneously immortalized breast cancer cell line, DHSF-BR16 cells, was isolated from the primary IDC of a 74-years old female patient, treated with neoadjuvant chemotherapy and disease-free 5-years after adjuvant chemotherapy. Primary breast cancer tissue surgically removed was classified as ER-/PR-/HER2+, and the same phenotype was maintained by DHSF-BR16 cells. We examined DHSF-BR16 cell morphology and relevant biological and molecular markers, as well as their response to anticancer drugs commonly used for breast cancer treatment. MCF-7 cells were used for comparison purposes. The DHSF-BR16 cells showed the ability to form spheroids and migrate. Furthermore, DHSF-BR16 cells showed a mixed stemness phenotype (i.e. CD44+/CD24-/low), high levels of cytokeratin 7, moderate levels of cytokeratin 8 and 18, EpCAM and E-Cadh. Transcriptome analysis showed 2071 differentially expressed genes between DHSF-BR16 and MCF-7 cells (logFC > 2, p-adj < 0.01). Several genes were highly upregulated or downregulated in the new cell line (log2 scale fold change magnitude within - 9.6 to + 12.13). A spontaneous immortalization signature, mainly represented by extracellular exosomes-, plasma membrane- and endoplasmic reticulum membrane pathways (GO database) as well as by metabolic pathways (KEGG database) was observed in DHSF-BR16 cells. Also, these cells were more resistant to anthracyclines compared with MCF-7 cells. Overall, DHSF-BR16 cell line represents a relevant model useful to investigate cancer biology, to identify both novel prognostic and drug response predictive biomarkers as well as to assess new therapeutic strategies.

Medicines for headache before and during pregnancy: a retrospective cohort study (ATENA study).

OBJECTIVE: To investigate headache treatment before and during pregnancy. BACKGROUND: Most headaches in pregnancy are primary disorders. Headaches are likely to ameliorate during pregnancy, although they may also begin or worsen. Most headache medications should be avoided during pregnancy because of potential fetal risks. However, only scarce evidence on headache drug consumption during pregnancy is available. DESIGN: ATENA was a retrospective, self-administered questionnaire-based, cohort study on women in either pregnancy or who have just delivered and reporting headache before and/or during pregnancy. RESULTS: Out of 271 women in either pregnancy or who have just delivered, 100 (37%) reported headache before and/or during pregnancy and constituted our study sample. Before pregnancy, the attitude toward the use of symptomatic drugs was characterized by both a strong focus on their safety and the willingness to avoid possible dependence from them. Compared to the year before, pregnancy led to changes in behavior and therapeutic habits as shown by a higher proportion of patients looking for information about drugs (44/100 [44%] vs. 36/100 [36%]) and a lower proportion of those treating headache attacks (88/100 [88%] vs. 52/100 [52%]) and by a lower use of nonsteroidal anti-inflammatory drugs (68/100 [68%] vs. 5/100 [5%]) and a much higher use of paracetamol (33/100 [33%] vs. 95/100 [95%]). CONCLUSIONS: Pregnancy changes how women self-treat their headache, and leads to search for information regarding drug safety, mostly due to the perception of fetal risk of drugs. Healthcare providers have to be ready to face particular needs of pregnant women with headache.

FGD3 Gene as a New Prognostic Factor in Breast Cancer.

Despite the establishment of the traditional prognostic factors for breast cancer, patients belonging to the same histological and molecular subgroup often present quite different outcomes. Recently, the introduction of gene expression profiling, assessed by RT-qPCR and microarray DNA analysis, offered a view of the whole cell gene activity and the ability to identify new transcripts that are associated with outcome. This review aimed to gather all recent trials about new breast cancer prognostic factors, focusing on the most promising one, the FGD3 gene, and to discuss the real feasibility of a molecular approach in everyday clinical practice. In conclusion, all literature concerning this subject indicated that expression of the FGD3 gene is a strong marker of good prognosis in breast cancer patients and that immunohistochemistry represents an efficient, inexpensive, reproducible evaluation method, affordable also by small Institutions.

Long-term Results After Neoadjuvant Chemotherapy for Breast Cancer: A Single-center Experience.

BACKGROUND/AIM: We evaluated the efficacy of neoadjuvant chemotherapy (NACT) in reducing locally-advanced breast cancer (LABC) size, thus improving breast-conserving surgery (BCS) rates, as well as its long-term outcome. PATIENTS AND METHODS: We analyzed 59 patients treated between 1999-2017 with NACT and subsequent surgery for LABC. RESULTS: We observed a tumor size reduction in 95% of cases, resulting in downstaging in 62.7%. The average tumor shrinkage was 49%. Women with a reduction in tumor size >50% after NACT had better 10-year OS rates than women with a reduction ≤50% (p=0.025). NACT allowed to perform BCS in 44% cases, whereas the remaining 56% cases underwent mastectomy. Overall, we observed recurrences in 37.2% patients. Recurrence rates after BCS and mastectomy were 30.7% (6 loco-regional and 2 distant cases) and 42.4% (5 loco-regional and 9 distant cases), respectively (p=0.07). CONCLUSION: NACT confirmed its effectiveness in reducing mastectomy rates by approximately 50%, without increasing the risk of local or distant recurrences.

Changing Trends in Mastectomy and Breast Reconstruction. Analysis of a Single-institution Experience Between 2004-2016.

BACKGROUND/AIM: Recently, "conservative" mastectomy with immediate breast reconstruction (M-R) has become the gold standard when the breast must be removed. We analyzed the evolution in the choice of mastectomy type in our Unit, focusing on factors associated with renounce to reconstruction and risk factors for its failure. PATIENTS AND METHODS: Clinical-pathological and surgical features of 132 patients who underwent mastectomy in our Unit from 2004 to 2016 were analyzed. M-R rate and different mastectomy techniques' rates between 2004-2009 and 2010-2016 were compared. RESULTS: M-R was associated with younger age at diagnosis (p<0.001) and early tumor stage (p=0.03). M-R rate increased from 49.1% to 72.2% (p=0.002) in the last years, with prominent use of nipple-sparing-mastectomy (p<0.001). M-R failure rate was associated with previous or subsequent irradiation/chemotherapy in 92.3% of cases. CONCLUSION: M-R and particularly nipple-sparing-mastectomy represented the standard in more recent years; reconstruction failure was associated with irradiation/chemotherapy, especially in implant-based reconstructions.

Expression of FGD3 gene as prognostic factor in young breast cancer patients.

The FGD3 gene works as a cell migration inhibitor and seems to be a promising indicator of outcome in some human cancers including breast. In this study, we analysed for the first time the prognostic role of FGD3 in young breast cancer patients. We studied the relationship between traditional prognostic factors, FGD3 expression and outcome in ≤40 years breast cancer patients. We found that lower FGD3 expression decreased the probability of disease-free survival (p = 0.042) and overall survival (p = 0.007). In a multivariate analysis for overall survival AJCC stage (p = 0.005) and FGD3 expression (p = 0.03) resulted independent prognostic factors. Low FGD3 expression increased the risk of death from disease (HR 5.73, p = 0.03). Moreover, low FGD3 expression was associated with more widespread lymph node involvement (p = 0.04) and a lower FGD3 staining intensity was found in positive-lymph-node patients vs negative (p = 0.003) and in patients with ≥10 involved lymph nodes vs <10 (p = 0.05). Our results suggest FGD3 to be a significant independent prognostic factor in young breast cancer patients in terms of disease-free survival and overall survival. A lower expression increased the risk of recurrence and death from disease and was associated with widespread lymph node metastases.

Day Surgery Management of Early Breast Cancer: Feasibility and Psychological Outcomes.

BACKGROUND/AIM: Breast cancer treatment represents a substantial amount of health-care costs and has a negative impact on womens' psychological health. Day-Surgery managment (DS) is a favorable alternative to a classic inpatient setting. In our prospective study we evaluated DS-treatment feasibility in terms of patient satisfaction, same-day-discharge rate, surgical-reintervention rate, psychological impact and costs. PATIENTS AND METHODS: We operated on 131 early breast cancer patients in DS. Surgical outcomes were evaluated. In 64 DS-treated breast cancer patients, psychological outcomes were analyzed using validated psychometric questionnaires and comparison was made with a corresponding group of women treated as inpatients. RESULTS: The same-day-discharge rate was 95.4%. No patient required readmission. The surgical-reintervention rate was 6.2%. DS-treatment significantly reduced anxiety (p=0.05) and depression (p=0.01) and afforded cost savings of 49%. CONCLUSION: DS-treatment of early breast cancer was feasible, with low reintervention rate, reduced anxiety and depression, high patients' satisfaction and substantial financial savings.

Corrigendum to "Role of Magnetic Resonance Imaging in the Preoperative Staging and Work-Up of Patients Affected by Invasive Lobular Carcinoma or Invasive Ductolobular Carcinoma".

[This corrects the article DOI: 10.1155/2018/1569060.].

Role of Magnetic Resonance Imaging in the Preoperative Staging and Work-Up of Patients Affected by Invasive Lobular Carcinoma or Invasive Ductolobular Carcinoma.

Purpose: The prevalence of invasive lobular carcinoma (ILC), the second most common type of breast cancer, accounts for 5%-15% of all invasive breast cancer cases. Its histological feature to spread in rows of single cell layers explains why it often fails to form a palpable lesion and the lack of sensitivity of mammography and ultrasound (US) to detect it. It also has a higher incidence of multifocal, multicentric, and contralateral disease when compared to the other histological subtypes. The clinicopathologic features and outcomes of Invasive Ductolobular Carcinoma (IDLC) are very similar to the ILC. The purpose of our study is to assess the importance of MRI in the preoperative management and staging of patients affected by ILC or IDLC. Materials and Methods: We identified women diagnosed with ILC or IDLC. We selected the patients who had preoperative breast MRI. For each patient we identified the areas of multifocal, multicentric, or contralateral disease not visible to standard exams and detected by preoperative MRI. We analyzed the potential correlation between additional cancer areas and histological cancer markers. Results: Of the 155 women who met our inclusion criteria, 93 (60%) had additional cancer areas detected by MRI. In 61 women, 39,4% of the overall population, the additional cancer areas were confirmed by US/tomosynthesis second look and biopsy. Presurgical MRI staging changed surgical management in the 37,4% of the patients. Only six patients of the overall population needed a reoperation after the initial surgery. No statistically significant correlation was found between MRI overestimation and the presence of histological peritumoral vascular/linfatic invasion. No statistically significant correlation was found between additional cancer areas and histological cancer markers. Conclusions: Our study suggests that MRI is an important tool in the preoperative management and staging of patients affected by lobular or ductolobular invasive carcinoma.

Stereotactic vacuum-assisted breast biopsy: Comparison between 11- and 8-gauge needles.

PURPOSE: The 11-gauge (11G) stereotactic vacuum-assisted breast biopsy (VABB) showed a better profile than 14G-VABB in terms of feasibility, safety, microcalcification sampling, and accuracy. Underestimation rates were significantly lower with 11G-VABB than with 14G-VABB. Thus, the introduction of an even larger needle at the VABB procedure could reduce this rate further. The purpose of this study was to compare the overall performance of stereotactic VABB with 8G and 11G needles. MATERIALS AND METHODS: Four hundred and three VABBs performed between July 2012 and February 2015 at the Breast Diagnostic Unit of Careggi Hospital in Florence were retrospectively analyzed; 197 were performed with 11G-VABB and 206 with 8G-VABB. Lesions were classified according to mammographical patterns in microcalcifications, architectural distortions, or opacities, and all biopsy targets were classified according to BIRADS classification as BIRADS III, IV or V. Data were collected on radiological classification of targets, imaging presentation, procedure time, number of specimens per procedure, and microcalcification retrieval on histological findings. Surgery was always performed when high-risk or malignant lesions (B3 or B5) were detected; the final diagnosis was made on surgical pathology. RESULTS: Compared to VABB with an 11G needle, 8G-VABB allows a reduction in the time needed to complete the procedure (20.6 versus 27.4, P < 0.00001) and the number of specimens collected per lesion (21.6 versus 12.2, P < 0.00001). Moreover, 8G-VABB resulted in the same diagnostic accuracy, and the underestimation rates were comparable between the two groups for both B3 and DCIS lesions. CONCLUSIONS: The 8G needle should be considered as a valid alternative option in VABB for breast lesions.