Accuracy of sentinel lymph node biopsy in male breast cancer: Systematic review and meta-analysis.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is commonly used in the surgical management of male breast cancer. Contrary to female breast cancer, limited data exist about its performance in male breast cancer. The objective of this systematic review and meta-analysis was to evaluate the SLNB accuracy in male breast cancer. METHODS: MEDLINE, EMBASE, Web of Science and The Cochrane Library were searched from January 1995 to April 2023 for studies evaluating the SLNB identification rate and false-negative rate in male breast cancer with negative preoperative axillary evaluation and primary surgery. For SLNB false-negative rate, the gold standard was the histology of axillary lymph node dissection (ALDN). Methodological quality was assessed by using the QUADAS-2 tool. Pooled estimates of the SLNB identification rate and false-negative rate were calculated. Heterogeneity of the pooled studies was evaluated using I2 index. RESULTS: A total of 12 retrospective studies were included. The 12 studies that reported the SLNB identification rate gathered a total of 164 patients; the 5 studies that reported the SLNB false-negative rate gathered a total of 50 patients with a systematic ALND. The pooled estimate of the SLNB identification rate was 99.0%. The SLNB false-negative rates were 0% in the 5 included studies and consequently so as the pooled estimate of the false-negative rate with no heterogeneity. CONCLUSION: SLNB for male breast cancer, following negative preoperative axillary assessment and primary surgery, appears feasible, consistent, and effective. Our research supports conducting immediate SLNB histological evaluation to facilitate prompt ALND in case of positive results.

Histological Risk Factors for Local Recurrence of Phyllodes Tumors of the Breast.

BACKGROUND/AIM: The rate of local recurrence (LR) of phyllodes tumor (PT) varies from 4 to 18%. Several histological risk factors of LR of PT are known. The aim of this study was to estimate the LR rate of PT according to PT grade and to evaluate histological risk factors of PT LR in our retrospective cohort. PATIENTS AND METHODS: This was a two-center study, conducted from 1995 to 2019. All patients with PT diagnosed on surgical specimen were included. PT was diagnosed histologically according to the grade category defined by the 2012 World Health Organization classification as benign, borderline or malignant PT. Univariate analysis and then multivariate logistic regression analysis were performed to determine histological risk factors of LR of PT. RESULTS: A total of 224 patients with PT were included: 152 with benign, 49 with borderline and 23 with malignant PT. The median and standard deviation for the duration of follow-up was 136.60 ± 167.43 months, and 18 patients (8.04%) developed LR: 7 (4.61%), 7 and (14.29%) and 4 (17.39%) with benign, borderline and malignant PT, respectively. In univariate analysis, LR was statistically increased for histological size ≥45 mm (p=0.003), borderline/malignant TP (p=0.006) and dense stromal cellularity (p<0.001). In multivariate analysis, only histological size ≥45 mm and cellularity were statistically associated with LR (odds ratio=1.83, 95% confidence interval=1.06-9.83, p=0.04; and odds ratio=3.69, 95% confidence interval=1.11-12.28, p=0.03, respectively). CONCLUSION: Histological size ≥45 mm and dense stromal cellularity were demonstrated as histological risk factors of LR of PT. In our cohort, no association was found between LR and PT grade nor LR and surgical margins ≥10 mm.

Negative Relationship between Post-Treatment Stromal Tumor-Infiltrating Lymphocyte (TIL) and Survival in Triple-Negative Breast Cancer Patients Treated with Dose-Dense Dose-Intense NeoAdjuvant Chemotherapy.

Background: Patients with triple-negative breast cancers (TNBC) have a poor prognosis unless a pathological complete response (pCR) is achieved after neoadjuvant chemotherapy (NAC). Few studies have analyzed changes in TIL levels following dose-dense dose-intense (dd-di) NAC. Patients and methods: From 2009 to 2018, 117 patients with TNBC received dd-di NAC at our institution. We aimed to identify factors associated with pre- and post-NAC TIL levels, and oncological outcomes relapse-free survival (RFS), and overall survival (OS). Results: Median pre-NAC and post-NAC TIL levels were 15% and 3%, respectively. Change in TIL levels with treatment was significantly correlated with metabolic response (SUV) and pCR. High post-NAC TIL levels were associated with a weak metabolic response after two cycles of NAC, with the presence of residual disease and nodal involvement at NAC completion. In multivariate analyses, high post-NAC TIL levels independently predicted poor RFS and poor OS (HR = 1.4 per 10% increment, 95%CI (1.1; 1.9) p = 0.014 and HR = 1.8 per 10% increment 95%CI (1.3−2.3), p < 0.0001, respectively). Conclusion: Our results suggest that TNBC patients with TIL enrichment after NAC are at higher risk of relapse. These patients are potential candidates for adjuvant treatment, such as immunotherapy, in clinical trials.

Ten-Year Outcomes of Hypofractionated Postmastectomy Radiation Therapy of 26 Gy in 6 Fractions.

PURPOSE: To investigate the efficacy and long-term side effects of hypofractionated postmastectomy radiation therapy (HFRT-PM) of 26 Gy in 6 fractions over 5 weeks. METHODS AND MATERIALS: We retrospectively reviewed characteristics and outcomes of patients with stage I to III breast cancer treated with HFRT-PM between 2000 and 2009. Treatment provided 4 fractions of 4 Gy (days 1, 3, 15, 17) and then 2 fractions of 5 Gy (days 29 and 31) over 5 weeks. The treatment techniques were applied by using 3-dimensional conformal radiation therapy of the chest wall with regional nodal volume if required. RESULTS: We identified 454 patients with a median follow-up of 10.6 years (range, 0.5-22.9). Regional nodal irradiation was done in 84.1% of patients. At 10 years, the cumulative incidence of locoregional relapse was 15.1%. In multivariate analysis, regional lymph node involvement (≥4 nodes) was associated with worse locoregional control (hazard ratio, 1.68; 95% confidence interval, 1.06-2.67; P = .03) and overall survival (hazard ratio, 2.16; 95% confidence interval, 1.59-2.95; P < .001). The toxicities were acceptable. The incidence of cardiac disorders (3.3%), and symptomatic lung fibrosis (1.5%) was low during follow-up. At 10 years, the cumulative rate of arm lymphedema was 9.5% and considered severe in 20 patients (4.4%). CONCLUSIONS: The long-term results of this study show that HFRT-PM of 26 Gy in 6 fractions over 5 weeks seems safe, but locoregional recurrence seems slightly higher than that observed in the literature, highlighting the need for long-term follow-up and for randomized trials for hypofractionated radiation therapy postmastectomy.

Intraoperative Radiotherapy for Breast Cancer in Elderly Women.

PURPOSE: To evaluate outcomes and postoperative toxicities after intraoperative radiotherapy (IORT) in elderly women. POPULATION: Women older than 65 years, with infiltrating ductal breast cancer ≤3 cm, expressing estrogen receptor (ER+) without Her2 overexpression, and with negative axillary nodes. TREATMENT: Treatment consisted of partial mastectomy with a sentinel lymph node biopsy (SLNB) procedure; in case of positive SLNB, IORT was cancelled. IORT consisted in a total dose of 20 Gy in 1 fraction delivered at the surface of the applicator with the Intrabeam® technique. RESULTS: IORT was planned to be administered to a total of 225 patients but was cancelled for 34 patients during surgery. Thus 191 patients were analyzed; mean age was 76 years, with 57 patients (30%) >80 years. Despite inclusion criteria, 15 had lobular carcinoma and 7 were triple negative. With a median follow-up of 40 months, we observed only 1 local recurrence, located in the skin over the initial tumor. The 5-year local relapse rate was 1.7%. A wound healing delay (>15 days) was observed in 21 patients (11%). Sixty-six patients (35%) had postoperative complications, mainly grade 2, resolving within a few days. Two patients needed surgical drainage for local abscesses. Long-term (>1 year) cosmetic outcome was evaluated in 120 patients and was judged excellent or good in 102 (91%). CONCLUSION: IORT can be safely given to elderly women, with a good local control rate and without major toxicities.

[A misleading breast metastasis of medullary thyroid carcinoma]. / Métastase mammaire d'un carcinome médullaire thyroïdien : un challenge diagnostique.

Recognition of mammary metastases by pathologists is fundamental because their prognosis and treatment are different from those of primary mammary carcinomas. We report the case of a 54-year-old woman presenting on her mammography a left breast nodule known for 5 years, having discreetly increased in size. Breast ultrasound showed a regular 1.2cm hypoechogenic nodular formation. A microbiopsy was performed. On microscopic examination, we observed a tumor proliferation realizing nests within a small, richly vascularized stroma. The tumor cells had a moderately abundant, eosinophilic, granular cytoplasm and a rounded, slightly atypical nucleus. One mitosis was found for 10 fields at×400 magnification. Tumor cells did not express hormone receptors but chromogranin A, synaptophysin, TTF1 and thyrocalcitonin. The proliferation index established by the anti-Ki67 antibody was 5 %. The diagnosis was a secondary localization of a well-differentiated neuroendocrine tumor which immunohistochemical profile firstly suggests a thyroid origin. We later learned that the patient had a history of total thyroidectomy 13 years ago. It was a sporadic medullary carcinoma of the thyroid. Bone scintigraphy revealed a lacunar lesion of the posterior part of the right iliac wing suspicious of secondary location. This right iliac lesion was biopsied. It was also a localization of the medullary thyroid carcinoma. The final diagnosis is a metastatic medullary thyroid carcinoma, slowly progressive, the mammary metastasis having probably existed for 5 years.

10-Year follow-up of 621 patients treated using high-dose rate brachytherapy as ambulatory boost technique in conservative breast cancer treatment.

PURPOSE: Breast conserving treatment, consisting of lumpectomy followed by whole-breast irradiation, is considered the standard of care in early-stage breast cancer. Randomized studies have reported that delivering boost doses to tumor bed improves local control rates, particularly in young women. This study sought to evaluate local control and cosmetic results of delivering boost doses using a high-dose-rate (HDR) brachytherapy (HDRBT) in breast cancer conservative treatment. METHODS: We included 621 T1-T2, N0-N1 breast cancer patients who underwent lumpectomy, external irradiation (44Gy over 5weeks), and a boost dose of two fractions of 5Gy to the tumor bed by means of HDR iridium brachytherapy. Implantation was performed during the lumpectomy or 2-3weeks after external irradiation. Population characteristics were as follows: pTis=11.6%; pT1=63.4%; pT2=25.0%; median tumor size=1.5cm; histology: ductal carcinoma in situ (DCIS): 72 (11.6%); infiltrative ductal carcinoma (IDC): 471 (75.8%); other: 78 (12.6%). For IDCs, the surgical margins were positive in 38cases (6.2%) and an extensive intraductal component was present in 254 cases. RESULTS: With a median follow-up of 10.3years, 47 local relapses were observed (10-year local relapse rate: 7.4%). Small-volume implantation (V100<45cc) and ductal carcinoma in situ histology both significantly correlated with local relapse. The 10-year overall survival was 91%. Cosmetic results were evaluated in 264patients, proving excellent in 58 (22%), good in 153 (58%), fair in 40 (15%), and poor in 13 (5%). CONCLUSIONS: Small implant volume and ductal carcinoma in situ histology significantly correlated with local relapse following HDR brachytherapy dose boost in breast cancer conservative treatment. Modern image-guided breast brachytherapy techniques using surgical clips as a guide may decrease potential treatment targeting errors, consequently improving local control without increasing toxicity.

Impact of radical surgery on outcome in locally advanced breast cancer patients without metastasis at the time of diagnosis.

BACKGROUND/AIM: In the era of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)FDG-PET/CT), more patients are being diagnosed with N3M0 disease. The objective of this study was to assess the prognostic impact of radical lymph node surgery (RLNS) in patients with locally advanced breast cancer classified as lymph node N3 disease according to the American Joint Committee on Cancer (AJCC) 2002 in whom there is no known distant metastasis and in the context of multimodal therapy. PATIENTS AND METHODS: This was a two-Center retrospective study that included patients with breast cancer classified as N3M0 after (18)FDG-PET/CT assessment. We reviewed the clinical characteristics, surgical treatment and oncological outcomes of those patients. RESULTS: Thirty-nine patients fulfilled the inclusion criteria. Multimodal treatment included neo-adjuvant chemotherapy (n=34), adjuvant radiotherapy (n=33), adjuvant chemotherapy (n=18) or neo- or adjuvant hormone therapy (n=17). Surgical treatment was not homogeneous. Eight patients had undergone RLNS and 31 conventional axillary lymph node dissection (CD). There was no significant difference in median overall survival between the RLNS group and the CD group (32 months (28-36) vs. 49 months (42-56) respectively (p=0.25)). The overall recurrence rate was 23%. Out of the 8 patients who had under gone RLNS, three had relapsed (two with distant metastases and one local). CONCLUSION: RLNS was not proven to be beneficial in our study. In order to guide surgical management for these patients, PET/CT and magnetic resonance imaging (MRI) could be of interest, therefore a pilot study to improve reproducible surgical management would be of interest.

Molecular apocrine breast cancers are aggressive estrogen receptor negative tumors overexpressing either HER2 or GCDFP15.

INTRODUCTION: Molecular apocrine (MA) tumors are estrogen receptor (ER) negative breast cancers characterized by androgen receptor (AR) expression. We analyzed a group of 58 transcriptionally defined MA tumors and proposed a new tool to identify these tumors. METHODS: We performed quantitative reverse transcription PCR (qRT-PCR) for ESR1, AR, FOXA1 and AR-related genes, and immunohistochemistry (IHC) for ER, PR, Human Epidermal Growth Factor Receptor 2 (HER2), CK5/6, CK17, EGFR, Ki67, AR, FOXA1 and GCDFP15 and we analyzed clinical features. RESULTS: MA tumors were all characterized by ESR1(-) AR(+) FOXA1(+) and AR-related genes positive mRNA profile. IHC staining on these tumors showed 93% ER(-), only 58% AR(+) and 90% FOXA1(+). 67% and 57% MA tumors were HER2(3+) and GCDFP15(+), respectively. Almost all MA tumors (94%) had the IHC signature HER2(3+) or GCDFP15(+) but none of the 13 control basal-like (BL) tumors did. Clinically, MA tumors were rather aggressive, with poor prognostic factors. CONCLUSION: MA tumors could be better defined by their qRT-PCR-AR profile than by AR IHC. In addition, we found that HER2 or GCDFP15 protein overexpression is a sensitive and specific tool to differentiate MA from BL in the context of ER negative tumors. A composite molecular and IHC signature could, therefore, help to identify MA tumors in daily practice.

Breast intracystic papillary carcinoma: an update.

Intracystic papillary carcinoma (IPC), a breast tumor mainly occuring in the elderly, has long been considered as a variant of ductal carcinoma in situ (DCIS). This is now debated since metastatic cases have been reported. In this study, surgical pieces of 20 IPCs were reassessed, and markers of myopepithelial layer (p63, CD10 and Smooth Muscle Actin) as well as estrogen receptors (ER) and progesterone receptors (PgR) and C-erb-B2 oncoprotein expression were systematically performed and quantified. In 10 cases, an associated unequivocal invasive component was found. In all 20 cases, no myoepithelial layer was found. Eighteen tumors were ER positive, 14 were PgR positive. Moreover, none of the tumors over-expressed C-erb-B2 oncoprotein. Therefore this study showed that in all cases of IPC there were microscopic features of invasive carcinoma despite good clinical prognostic indicators, and that precise characterization of tumors requires extensive paraffin embedding of surgical pieces.