Predictive markers for pathological complete response after neo-adjuvant chemotherapy in triple-negative breast cancer.

A combination of Sox10 and GATA3 was previously identified as a marker for metastatic triple-negative breast cancer (TNBC), but it is uncertain whether their expression is associated with pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). This study investigates the predictive value of clinicopathological characteristics, as well as protein expression of Sox10, GATA3, p53 and p63, in a consecutive series of TNBC patients treated with NAC. Archived hematoxylin & eosin stained slides of core biopsies and resection specimens from 35 TNBC patients were reviewed. The following clinicopathological characteristics were determined at the biopsy level: age at diagnosis, cancer type, Nottingham grade, lympho-vascular invasion, syncytial growth, necrosis, clear cell differentiation, myxoid peritumor stroma, stromal tumor-infiltrating lymphocytes (sTILs) and presence of an in situ component. The MD Anderson residual cancer burden (RCB) score and corresponding RCB class were determined. Immunohistochemistry for Sox10, p53, GATA3 and p63 was performed at the biopsy level. sTILs, either as a continuous or as a dichotomous variable, were the only parameter that was significantly associated with pCR in univariable and multivariable analyses. Assessment of sTILs showed moderate to good interobserver agreement. High sTILs (≥40%) were significantly associated with increased pCR rates, and this association was observer-independent. This retrospective study of a consecutive community-based cohort of TNBC patients confirms that sTILs are a robust, observer-independent predictor for therapeutic response after NAC. The combination of Sox10, GATA3 and p53 immunoreactivity is unlikely to harbor any predictive value for pCR in TNBC.

Uterine fibroid management: Today and tomorrow.

Current treatments for fibroids are mainly surgical and expensive, so alternatives need to be found. It is, therefore, vital to develop and evaluate alternatives to surgical procedures, especially when fertility preservation is the goal. Selective progesterone receptor modulators (SPRMs) are synthetic compounds that have either an agonistic or antagonistic impact on target tissues determined by their binding to progesterone receptors. Their mixed activity depends on recruitment of cofactors that regulate transcription along so-called genomic pathways, as well as nongenomic interactions with other signaling pathways. There is no doubt that surgery remains indicated in some instances, but we must now establish whether use of SPRMs (notably ulipristal acetate) allows less invasive surgery or even complete avoidance of surgery. Long-term intermittent administration of ulipristal acetate will undoubtedly change our approach to the management of uterine fibroids according to the International Federation of Gynecology and Obstetrics classification, which provides a comprehensive basis for different treatment options. When considering less invasive techniques (uterus-sparing options like myomectomy), the choice is guided by the size, number and location of fibroids, as well as the personal experience of the gynecologist and available equipment. There is now a growing body of evidence pointing to the crucial role of progesterone pathways in the pathophysiology of uterine fibroids. SPRMs should, therefore, be considered an alternative to surgical therapy, or at least an adjunct to surgery, as illustrated in the algorithms. © 2019 Japan Society of Obstetrics and Gynecology.

Multimodality Imaging of Pelvic Inflammatory Disease Complicated with Tubo-Ovarian Abscess.

Teaching Point: Pelvic inflammatory disease (PID) is the most frequent gynecologic cause of emergency visits. Because of its prevalence and non-specific symptoms, the radiologist may encounter this pathology and its complications on all imaging modalities and should carefully assess PID signs to avoid delay in management, late complications, and unnecessary surgery.

Prolapsed Uterine Fibroid: Value of MRI in Case of Massive Bleeding.

Teaching Point: In case of acute bleeding caused by a mass located in the vagina, it may be difficult to assess the origin of the mass and determine whether it is benign or malignant; MRI is a useful tool for mass detection, diagnosis, and treatment decision.

Predictive Biomarkers of Response to Neoadjuvant Chemotherapy in Breast Cancer: Current and Future Perspectives for Precision Medicine.

Pathological complete response (pCR) after neoadjuvant chemotherapy in patients with early breast cancer is correlated with better survival. Meanwhile, an expanding arsenal of post-neoadjuvant treatment strategies have proven beneficial in the absence of pCR, leading to an increased use of neoadjuvant systemic therapy in patients with early breast cancer and the search for predictive biomarkers of response. The better prediction of response to neoadjuvant chemotherapy could enable the escalation or de-escalation of neoadjuvant treatment strategies, with the ultimate goal of improving the clinical management of early breast cancer. Clinico-pathological prognostic factors are currently used to estimate the potential benefit of neoadjuvant systemic treatment but are not accurate enough to allow for personalized response prediction. Other factors have recently been proposed but are not yet implementable in daily clinical practice or remain of limited utility due to the intertumoral heterogeneity of breast cancer. In this review, we describe the current knowledge about predictive factors for response to neoadjuvant chemotherapy in breast cancer patients and highlight the future perspectives that could lead to the better prediction of response, focusing on the current biomarkers used for clinical decision making and the different gene signatures that have recently been proposed for patient stratification and the prediction of response to therapies. We also discuss the intratumoral phenotypic heterogeneity in breast cancers as well as the emerging techniques and relevant pre-clinical models that could integrate this biological factor currently limiting the reliable prediction of response to neoadjuvant systemic therapy.

Effects of Hormones on Breast Development and Breast Cancer Risk in Transgender Women.

Transgender women experience gender dysphoria due to a gender assignment at birth that is incongruent with their gender identity. Transgender people undergo different surgical procedures and receive sex steroids hormones to reduce psychological distress and to induce and maintain desired physical changes. These persons on feminizing hormones represent a unique population to study the hormonal effects on breast development, to evaluate the risk of breast cancer and perhaps to better understand the precise role played by different hormonal components. In MTF (male to female) patients, hormonal treatment usually consists of antiandrogens and estrogens. Exogenous hormones induce breast development with the formation of ducts and lobules and an increase in the deposition of fat. A search of the existing literature dedicated to hormone regimens for MTF patients, their impact on breast tissue (incidence and type of breast lesions) and breast cancer risk provided the available information for this review. The evaluation of breast cancer risk is currently complicated by the heterogeneity of administered treatments and a lack of long-term follow-up in the great majority of studies. Large studies with longer follow-up are required to better evaluate the breast cancer risk and to understand the precise mechanisms on breast development of each exogenous hormone.

BRCA1 Mutation: An Insidious Enemy with Multiple Facets .

Epidemiological studies suggest that around 10% of breast cancers are due to hereditary predisposition. The risk of cancer is exponentially increased in patients harboring BRCA1 or BRCA2 mutations. Cumulative breast cancer risk by age 80 is estimated to 72% for BRCA1 mutation carriers and 69% for BRCA2. The cumulative risk estimates for developing ovarian cancer by age 80 are 44% for BRCA1 mutation carriers and 17% for BRCA2. We present here the case of a 59-year-old woman who developed a left breast cancer in 2014 treated by conservative surgery, radiotherapy, and endocrine therapy with letrozole. The diagnosis of BRCA1 mutation was performed in 2015. In 2018, the patient was referred to our institution for treatment of an aggressive angiosarcoma developed in the same breast. She had undergone radical hysterectomy by the age of 49 years for a benign uterine pathology. In 2020, she developed a tumor in the gastric wall; histological analysis confirmed a serous papillary carcinoma of ovarian origin. She was treated - after gastrectomy and lymphadenectomy - with 6 courses of carboplatin and paclitaxel followed by olaparib therapy. In 2021, she suffered from a chest recurrence of high grade angiosarcoma. New resection with free margins was performed. We discuss the link between angiosarcomas and BRCA mutations, the therapeutic options for angiosarcoma and ovarian cancer of extra ovarian origin and the follow-up modalities.

Morphological intratumor heterogeneity in ductal carcinoma in situ of the breast.

Ductal carcinoma in situ (DCIS) of the breast is a heterogeneous disease in terms of morphological characteristics, protein expression profiles, genetic abnormalities, and potential for progression. Molecular heterogeneity has been extensively studied in DCIS. Yet morphological heterogeneity remains relatively undefined. This study investigated morphological intratumor heterogeneity in a series of 51 large DCIS. Nuclear atypia, DCIS architecture, necrosis, calcifications, stromal architecture, and stromal inflammation were assessed in one biopsy slide and three representative slides from each corresponding resection. For each histopathological feature, a histo-score was determined per slide and compared between the biopsy and the resection, as well as within a single resection. Statistical analysis comprised of Friedman tests, post hoc Wilcoxon tests with Bonferroni corrections, Mann-Whitney U tests, and chi-square tests. Despite substantial morphological heterogeneity in around 50% of DCIS, the histopathological assessment of the biopsy did not statistically significantly differ from the resection. Morphological heterogeneity was not significantly associated with patient age, DCIS size, or type of surgery, except for a weak association between heterogeneous stromal inflammation and smaller DCIS size. At the group level, the degree of heterogeneity did not significantly affect the representativity of a biopsy. At the individual patient level, however, the presence of necrosis, intraductal calcifications, myxoid stromal changes, and high-grade nuclear atypia was underestimated in a minority of DCIS patients. This study confirms the presence of morphological heterogeneity in DCIS for all six evaluated histopathological features. This should be kept in mind when taking biopsy-based treatment decisions for DCIS patients.

Non-Puerperal Uterine Inversion.

We report a case of non-puerperal uterine inversion, illustrating the correlation between MRI and pre-operation macroscopic images.

Breast tuberculosis imaging.

We report unusual magnetic resonance images of breast tuberculosis before and after treatment. Magnetic resonance imaging may assess the efficiency of treatment of breast tuberculosis.