Metabolic adaptation towards glycolysis supports resistance to neoadjuvant chemotherapy in early triple negative breast cancers.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is the standard of care for patients with early-stage triple negative breast cancers (TNBC). However, more than half of TNBC patients do not achieve a pathological complete response (pCR) after NAC, and residual cancer burden (RCB) is associated with dismal long-term prognosis. Understanding the mechanisms underlying differential treatment outcomes is therefore critical to limit RCB and improve NAC efficiency. METHODS: Human TNBC cell lines and patient-derived organoids were used in combination with real-time metabolic assays to evaluate the effect of NAC (paclitaxel and epirubicin) on tumor cell metabolism, in particular glycolysis. Diagnostic biopsies (pre-NAC) from patients with early TNBC were analyzed by bulk RNA-sequencing to evaluate the predictive value of a glycolysis-related gene signature. RESULTS: Paclitaxel induced a consistent metabolic switch to glycolysis, correlated with a reduced mitochondrial oxidative metabolism, in TNBC cells. In pre-NAC diagnostic biopsies from TNBC patients, glycolysis was found to be upregulated in non-responders. Furthermore, glycolysis inhibition greatly improved response to NAC in TNBC organoid models. CONCLUSIONS: Our study pinpoints a metabolic adaptation to glycolysis as a mechanism driving resistance to NAC in TNBC. Our data pave the way for the use of glycolysis-related genes as predictive biomarkers for NAC response, as well as the development of inhibitors to overcome this glycolysis-driven resistance to NAC in human TNBC patients.

Pregnancy After Breast Cancer in Young BRCA Carriers: An International Hospital-Based Cohort Study.

Importance: Young women with breast cancer who have germline pathogenic variants in BRCA1 or BRCA2 face unique challenges regarding fertility. Previous studies demonstrating the feasibility and safety of pregnancy in breast cancer survivors included limited data regarding BRCA carriers. Objective: To investigate cumulative incidence of pregnancy and disease-free survival in young women who are BRCA carriers. Design, Setting, and Participants: International, multicenter, hospital-based, retrospective cohort study conducted at 78 participating centers worldwide. The study included female participants diagnosed with invasive breast cancer at age 40 years or younger between January 2000 and December 2020 carrying germline pathogenic variants in BRCA1 and/or BRCA2. Last delivery was October 7, 2022; last follow-up was February 20, 2023. Exposure: Pregnancy after breast cancer. Main Outcomes and Measures: Primary end points were cumulative incidence of pregnancy after breast cancer and disease-free survival. Secondary end points were breast cancer-specific survival, overall survival, pregnancy, and fetal and obstetric outcomes. Results: Of 4732 BRCA carriers included, 659 had at least 1 pregnancy after breast cancer and 4073 did not. Median age at diagnosis in the overall cohort was 35 years (IQR, 31-38 years). Cumulative incidence of pregnancy at 10 years was 22% (95% CI, 21%-24%), with a median time from breast cancer diagnosis to conception of 3.5 years (IQR, 2.2-5.3 years). Among the 659 patients who had a pregnancy, 45 (6.9%) and 63 (9.7%) had an induced abortion or a miscarriage, respectively. Of the 517 patients (79.7%) with a completed pregnancy, 406 (91.0%) delivered at term (≥37 weeks) and 54 (10.4%) had twins. Among the 470 infants born with known information on pregnancy complications, 4 (0.9%) had documented congenital anomalies. Median follow-up was 7.8 years (IQR, 4.5-12.6 years). No significant difference in disease-free survival was observed between patients with or without a pregnancy after breast cancer (adjusted hazard ratio, 0.99; 95% CI, 0.81-1.20). Patients who had a pregnancy had significantly better breast cancer-specific survival and overall survival. Conclusions and Relevance: In this global study, 1 in 5 young BRCA carriers conceived within 10 years after breast cancer diagnosis. Pregnancy following breast cancer in BRCA carriers was not associated with decreased disease-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03673306.

Tumor sequencing is useful to refine the analysis of germline variants in unexplained high-risk breast cancer families.

BACKGROUND: Multigene panels are routinely used to assess for predisposing germline mutations in families at high breast cancer risk. The number of variants of unknown significance thereby identified increases with the number of sequenced genes. We aimed to determine whether tumor sequencing can help refine the analysis of germline variants based on second somatic genetic events in the same gene. METHODS: Whole-exome sequencing (WES) was performed on whole blood DNA from 70 unrelated breast cancer patients referred for genetic testing and without a BRCA1, BRCA2, TP53, or CHEK2 mutation. Rare variants were retained in a list of 735 genes. WES was performed on matched tumor DNA to identify somatic second hits (copy number alterations (CNAs) or mutations) in the same genes. Distinct methods (among which immunohistochemistry, mutational signatures, homologous recombination deficiency, and tumor mutation burden analyses) were used to further study the role of the variants in tumor development, as appropriate. RESULTS: Sixty-eight patients (97%) carried at least one germline variant (4.7 ± 2.0 variants per patient). Of the 329 variants, 55 (17%) presented a second hit in paired tumor tissue. Of these, 53 were CNAs, resulting in tumor enrichment (28 variants) or depletion (25 variants) of the germline variant. Eleven patients received variant disclosure, with clinical measures for five of them. Seven variants in breast cancer-predisposing genes were considered not implicated in oncogenesis. One patient presented significant tumor enrichment of a germline variant in the oncogene ERBB2, in vitro expression of which caused downstream signaling pathway activation. CONCLUSION: Tumor sequencing is a powerful approach to refine variant interpretation in cancer-predisposing genes in high-risk breast cancer patients. In this series, the strategy provided clinically relevant information for 11 out of 70 patients (16%), adapted to the considered gene and the familial clinical phenotype.

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.

A non-randomized dose-escalation Phase I trial of a protein-based immunotherapeutic for the treatment of breast cancer patients with HER2-overexpressing tumors.

This Phase I dose-escalation study (NCT00058526) assessed the safety and immunogenicity of an anti-cancer immunotherapeutic (recombinant HER2 protein (dHER2) combined with the immunostimulant AS15) in patients with early-stage HER2-overexpressing breast cancer (BC). Sixty-one trastuzumab-naive patients with stage II-III HER2-positive BC received the dHER2 immunotherapeutic after surgical resection and adjuvant therapy. They were allocated into four cohorts receiving different doses of dHER2 (20, 100, 500 µg) combined with a fixed AS15 dose. Safety and immunogenicity (dHER2-specific antibody responses) were assessed. After completing the immunization schedule (three or six doses over 14 weeks) and a six-month follow-up, the patients were followed for 5 years for late toxicity, long-term immunogenicity, and clinical status. The immunizations were well tolerated, and increasing doses of dHER2 had no impact on the frequency or severity of adverse events. Few late toxicities were reported, and after 5 years 45/54 patients (83.3 %) were still alive, while 28/45 (62 %) with known disease status were disease free. Regarding the immunogenicity of the compound, a positive association was found between the dHER2 dose, the immunization schedule, and the prevalence of dHER2-specific humoral responses. Among the patients receiving the most intense immunization schedule with the highest dHER2 dose, 6/8 maintained their dHER2-specific antibody response 5 years after immunization. The dHER2 immunotherapeutic had an acceptable safety profile in early HER2-positive BC patients. dHER2-specific antibody responses were induced, with the rate of responders increasing with the dHER2 dose and the number and frequency of immunizations.

Risk perception of patients with ductal carcinoma in situ (DCIS) of the breast and their healthcare practitioners: The importance of histopathological terminology, and the gaps in our knowledge.

Despite ductal carcinoma in situ (DCIS) being a non-obligatory precursor of invasive breast carcinoma, its diagnosis generates substantial psychological distress. The limited knowledge about the natural history of DCIS contributes to the insufficient transmission of information about DCIS to patients and the general population. The uncertainty about the progression risk to invasive carcinoma hampers adequate communication by clinicians. Breast cancer-related mortality after a DCIS diagnosis is low. However, several studies have demonstrated that DCIS patients generally overestimate the risk of developing loco-regional recurrence or dying from breast cancer. Various factors contribute to this perceived risk. Despite the lack of infiltrative growth, DCIS is treated similarly to invasive breast cancer, with surgery, radiotherapy, and hormonal therapy. Additionally, the term 'carcinoma' in DCIS provokes anxiety. Incorrect risk perception by physicians may result in overtreatment. Here, we provide an overview of epidemiologic data on mortality after DCIS. We discuss the impact of the term 'ductal carcinoma in situ' on patients' and physicians' perceptions of risk. The available evidence is mostly limited to patients within the Anglosphere. Recent studies, and European studies in particular, are scarce. We identify this as an area of interest for future large-scale European studies. We discuss the potential value of the "ductal intraepithelial neoplasia" (DIN) terminology, introduced in 1998. Although replacing the concept of 'DCIS' with the DIN terminology is unlikely to solve the entire problem of risk overestimation, it could be the first step to optimize doctor-patient communication and alter the current risk perception.

Cardiac structure, function, and coronary anatomy 10 years after isolated contemporary adjuvant radiotherapy in breast cancer patients with low cardiovascular baseline risk.

AIMS: The effects of isolated contemporary low-dose breast cancer (BC) radiotherapy (RT) on the heart remain poorly understood. This study aims to assess the long-term impacts of BC-RT on cardiac structure and function. METHODS AND RESULTS: Seventy-six women (62 ± 7 years) without history of prior heart disease, who had undergone RT for either first left (n = 36) or right (n = 40) BC, without additional medical oncology therapy apart from hormonal treatment 11 ± 1 years earlier, underwent transthoracic echocardiography, cardiac magnetic resonance imaging (CMR), computed tomography coronary angiography (CTCA), NT-proBNP, and a 6-min walk test (6MWT). They were compared with 54 age-matched healthy female controls. By CTCA, 68% of BC patients exhibited no or very mild coronary disease, while only 11% had moderate stenosis (50-69%) and 3% had significant stenosis (>70%). Despite slightly reduced regional echocardiographic midventricular strains, BC patients exhibited similar global left and right ventricular volumes, ejection fractions, and global strains by echocardiography and CMR as controls. Mitral E/e' ratios were slightly higher, and mitral deceleration times were slightly lower, but NT-proBNP was similar to controls. Also, 6MWT was normal. None had late gadolinium enhancement, and extracellular volume fraction was similar in BC (28 ± 3 vs. 29 ± 3, P = 0.15) and controls. No differences were observed relative to dose or side of RT. CONCLUSION: Aside from minor alterations of regional strains and diastolic parameters, women who received isolated RT for BC had low prevalence of coronary disease, normal global systolic function, NT-proBNP, and exercise capacity and showed no structural changes by CMR, refuting significant long-term cardiotoxicity in such low-risk patients.

Predictive markers for pathological complete response (pCR) after neo-adjuvant chemotherapy in HER2-positive breast carcinoma.

OBJECTIVES: Patients with HER2-positive invasive breast cancer that is node-positive and/or larger than 3 cm are generally treated with neoadjuvant chemotherapy (NAC). We aimed to identify predictive markers for pathological complete response (pCR) after NAC in HER2-positive breast carcinoma. METHODS: Hematoxylin/eosin-stained slides of 43 HER2-positive breast carcinoma biopsies were histopathologically reviewed. Immunohistochemistry (IHC) was performed on pre-NAC biopsies, comprising HER2, estrogen receptor (ER), progesterone receptor (PR), Ki-67, epidermal growth factor receptor (EGFR), mucin-4 (MUC4), p53 and p63. Dual-probe HER2 in situ hybridization (ISH) was performed to study the mean HER2 and CEP17 copy numbers. ISH and IHC data were retrospectively collected for a validation cohort, comprising 33 patients. RESULTS: Younger age at diagnosis, 3+ HER2 IHC scores, high mean HER2 copy numbers and high mean HER2/CEP17 ratios were significantly associated with an increased chance of achieving a pCR, and the latter two associations were confirmed in the validation cohort. No other immunohistochemical or histopathological markers were associated with pCR. CONCLUSIONS: This retrospective study of two community-based NAC-treated HER2-positive breast cancer patient cohorts identified high mean HER2 copy numbers as a strong predictor for pCR. Further studies on larger cohorts are required to determine a precise cut-point for this predictive marker.

Neutrophil:lymphocyte ratio and intraoperative use of ketorolac or diclofenac are prognostic factors in different cohorts of patients undergoing breast, lung, and kidney cancer surgery.

BACKGROUND: Inflammation is associated with a worse outcome in cancer and neutrophil:lymphocyte ratio (NLR) is a strong prognostic value. In cancer, nonsteroidal anti-inflammatory drugs (NSAIDs) could be of interest. We investigated the prognostic significance of NLR and the impact of intraoperative NSAIDs in cancer surgeries. METHODS: We performed an observational study in early breast, kidney, and lung cancers (357, 227, and 255 patients) with uni- and multivariate analyses (Cox model). RESULTS: In breast cancer (Centre 1), NLR ≥ 4 is associated with a higher risk of relapse (hazards ratio (HR) = 2.41; 95 % confidence interval (CI) 1.01-5.76; P = 0.048). In breast cancer (Centre 2), NLR ≥ 3 is associated with a higher risk of relapse (HR = 4.6; 95 % CI 1.09-19.1; P = 0.04) and higher mortality (HR = 4.0; 95 % CI 1.12-14.3; P = 0.03). In kidney cancer, NLR ≥ 5 is associated with a higher risk of relapse (HR = 1.63; 95 % CI 1.00-2.66; P = 0.05) and higher mortality (HR = 1.67; 95 % CI 1.0-2.81; P = 0.05). In lung cancer, NLR ≥ 5 is associated with higher mortality (HR = 1.45; 95 % CI 1.02-2.06; P = 0.04). The intraoperative use of NSAIDs in breast cancer patients (Centre 1) is associated with a reduced recurrence rate (HR = 0.17; 95 % CI 0.04-0.43; P = 0.0002) and a lower mortality (HR = 0.25; 95 % CI 1.08-0.75; P = 0.01). NSAIDs use at the beginning of the surgery is independently associated with a lower metastases risk after lung cancer surgery (HR = 0.16; 95 % CI 0.04-0.63; P = 0.009). Ketorolac use is independently associated with longer survival (HR = 0.55; 95 % CI 0.31-0.95; P = 0.03). CONCLUSIONS: In these cohorts, these analyses show that NLR is a strong perioperative prognosis factor for breast, lung, and kidney cancers. In this context, intraoperative NSAIDs administration could be associated with a better outcome.

Breast Development and Cancer.

The human breast, as mentioned by Gudjonsson and co-authors [...].

Breast-implant Related Silicone Lymphadenopathy: Asteroid Bodies do not Always Equal Sarcoidosis!

Silicone breast implants are frequently used for breast augmentation for cosmetic purposes, as well as for breast reconstruction after prophylactic or therapeutic mastectomy. Silicone lymphadenopathy is a well-known complication of silicone breast implants. Silicone droplets are present in the breast tissue through 'silicone bleeding' of the implant or because of implant rupture. These silicone particles can migrate from the breast to the regional lymph nodes. Silicone lymphadenopathy is caused by a substantial foreign body reaction against these silicone particles, and is frequently associated with asteroid body-containing multinucleated giant cells. Similar multinucleated giant cells are often observed in the capsule surrounding the silicone breast implant, and the number of associated asteroid bodies is highly variable. Here, we discuss a series of twelve women with breast implant-related asteroid bodies in their lymph nodes and/or breast tissue. This pictorial essay illustrates that the presence of asteroid bodies in a lymph node does not necessarily suggests a diagnosis of sarcoidosis. Clinical information about the patient having (or having had) silicone breast implants is often lacking. The encounter of asteroid body-containing giant cells in lymph node cytology, biopsies or resections should therefore lead to reflex clinical-pathological correlation, before establishing a final diagnosis.

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.

Artefactual Epithelial Displacement in a Papilloma with Extensive Usual Duct Hyperplasia Mimics a Solid Papillary Carcinoma with Invasive Growth.

Mammary solid papillary carcinoma and usual duct hyperplasia (UDH) of the breast are morphological look-alikes, characterized by cellular streaming, solid growth, and a lack of high-grade nuclear atypia. Here, we report a challenging papillary lesion in the breast of a 48-year-old woman that presented with a double pitfall. A core needle biopsy showed a solid papillary proliferation of epithelial cells with oval to round overlapping nuclei, surrounded by a sclerotic stroma. This distorted lesion contained peripheral clefts and cellular streaming, without high-grade nuclear atypia. Immunohistochemistry showed diffuse heterogenous immunoreactivity for estrogen receptor and cytokeratin 5, and no immunoreactivity for chromogranin and synaptophysin. The immunohistochemical profile distinguished this sclerosed papilloma with extensive UDH from a solid papillary carcinoma. The lumpectomy specimen revealed a second challenge, where multiple epithelial islets without surrounding myoepithelial cells were observed near the papilloma, mimicking an invasive carcinoma. These islets displayed the same immunohistochemical profile as the sclerosed papilloma and they were surrounded by steatonecrosis and reactive fibroblasts, indicating epithelial displacement within the biopsy needle tract. A sclerosed papilloma with extensive UDH is a morphologically challenging mimic of a solid papillary carcinoma. Immunohistochemistry is helpful to distinguish both entities from one another. Extensive epithelial displacement in the biopsy tract made this case particularly challenging, as the displaced epithelial islets mimicked an invasive carcinoma. Pathologists should be aware of this uncommon double pitfall to prevent misdiagnosis.

Periductal Stromal Tumors and Phyllodes Tumors Represent a Spectrum of Fibroepithelial Lesions: What Is in a Name?

Periductal stromal tumors (PSTs) of the breast are considered as a rare subtype of phyllodes tumors. These rare fibroepithelial lesions display a biphasic morphology, characterized by a cellular stroma surrounding benign ducts. Unlike phyllodes tumors, they do not present with a leaflike architecture, rendering a biopsy diagnosis of a PST very challenging. In this report, we compare the histopathological features of a PST with those of a borderline phyllodes tumor. We discuss the differences and similarities between both entities, and we highlight the potential pitfalls of the respective biopsies. Both cases illustrate that PSTs and phyllodes tumors are part of the same spectrum. This biological spectrum implies that "hybrid" lesions do exist, which can be hard to classify.

Severe Gestational Gigantomastia: from Mastectomy to Staged Autologous Breast Reconstruction. A Case Report.

Gestational gigantomastia (GGM) is a rare condition characterized by a massive overgrowth of breast tissue during pregnancy. Surgical sanction may be required when conservative measures fail. In this study, we report the case of a 29-year-old woman who presented with an evolutive GGM responsible for physical and emotional distress, despite medical treatment. A multidisciplinary decision was made to induce delivery at 32 weeks. In the postdelivery period, the patient developed breast wounds, complicated with septic cardiomyopathy. An emergency bilateral mastectomy was then carried out, together with banking of both nipple-areola complexes. Thereafter, delayed bilateral 2-stage breast reconstruction was started at 12 months with subcutaneous tissue expanders, later on followed by implants removal and autologous reconstruction with bilateral deep inferior epigastric artery perforator flaps and bilateral nipple replantation.

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.

Hypnosis Sedation Reduces the Duration of Different Side Effects of Cancer Treatments in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy.

BACKGROUND: Reducing side effects of cancer treatments is a major challenge for clinicians involved in the management of breast cancer patients. METHODS: We analyzed data from 63 patients (32 in the general anesthesia group and 31 in the hypnosis sedation group) who were included in 1 prospective non-randomized trial evaluating hypnosis sedation in breast cancer treatment. The patients were followed every 3 months for 2 years. All patients received neoadjuvant chemotherapy with 4 cycles of epirubicin and cyclophosphamide followed by taxanes. Thereafter, patients underwent surgery while on general anesthesia or while on hypnosis sedation. Radiotherapy was administered according to institutional guidelines. Endocrine therapy was prescribed if tumors expressed hormone receptors. Prevalence, intensity and duration of polyneuropathy, musculoskeletal pain, postoperative pain and cancer-related fatigue were assessed at each medical visit. RESULTS: Symptoms duration was statistically reduced for polyneuropathy (p < 0.05), musculoskeletal pain (p < 0.05) postoperative pain and cancer-related fatigue (p < 0.05) in the hypnosis group. CONCLUSION: Despite the limitations of this study (lack of randomization and small size) we conclude that hypnosis sedation may exert a role on different side effects of breast cancer treatment in patients receiving neoadjuvant chemotherapy, mainly by reducing their duration.

Do intraoperative analgesics influence breast cancer recurrence after mastectomy? A retrospective analysis.

BACKGROUND: Whether intraoperative analgesics have an impact on postoperative cancer recurrence is unknown. Some investigations suggest that the opioids could favor relapse and that regional analgesia and nonsteroidal antiinflammatory drugs could improve cancer prognosis. We retrospectively reviewed our series of breast cancer surgery patients. METHODS: This retrospective study included 327 consecutive women who underwent mastectomy with axillary dissection for breast cancer. The main objective was to compare the incidence of cancer recurrence among patients who received different analgesics during surgery. RESULTS: Perioperative characteristics, cancer prognostic factors, and the length of surgery were comparable regardless of the analgesics administered. Univariate and multivariate analyses showed a lower cancer recurrence rate when ketorolac was given before surgery (P = 0.019). Other analgesics (sufentanil, ketamine, and clonidine) were not associated with a significant reduction in cancer recurrence rates in our series. CONCLUSION: This retrospective analysis suggests that intraoperative administration of ketorolac decreases the risk of breast cancer relapse compared with other analgesícs.