Glycogen Rich Clear Cell Carcinoma (GRCC) of the breast may not have a poor prognosis

IntroductionGlycogen Rich Clear Cell Carcinoma (GRCC) is a rare variant of breast carcinomas and believed to be linked with a poor prognosis.Case summaryWe are presenting a 60-year-old Saudi lady with a 2 cm GRCC carcinoma associated with clear cell ductal carcinoma in situ (DCIS) and no axillary lymph node involvement. The tumor was Estrogen and Progesterone receptors (ER & PR) positive and HER 2-neu negative. She underwent mastectomy with sentinel lymph node biopsy followed by hormonal therapy. She is alive and free of disease for 35 months.ConclusionThe prognosis of GRCC may not be different from other types of invasive breast cancer.     

Invasive Micropapillary Carcinoma of the Breast: A Clinicopathologic Study of 103 Cases of an Unusual and Highly Aggressive Variant of Breast Carcinoma

Invasive micropapillary carcinoma (IMPC) of the breast is an uncommon, highly aggressive breast cancer that may occur in pure and mixed forms. Our aim in this study is to investigate the relationship between clinical, histopathologic, and immunohistochemical features of pure and mixed IMPC cases diagnosed and treated at our institution. One hundred and three IMPC cases diagnosed at our institution over a period of 19 years have been selected. Clinical, histopathologic features, as well as hormone status and c‐erb‐B2 overexpression of tumors were re‐evaluated. Mann–Whitney U, chi‐squared, Kaplan–Meier, and Fisher's exact tests were used for statistical analyses. Results were considered to be significant at p < 0.05. Twenty cases (19.4%) were pure, and 83 cases (80.6%) were mixed IMPC. The most common nonmicropapillary invasive carcinoma component in mixed cases was invasive ductal carcinoma (IDC; 78.3%). Progesterone receptor was significantly less positive in pure IMPC cases (p = 0.031). There was no statistically significant difference between the two groups, in terms of mean age of the patients (53.0 versus 52.8), mean tumor size (26.6 mm versus 27.7 mm), presence of high‐grade tumor (p = 0.631), presence of sentinel lymph node (SN) metastasis (p = 1.000), axillary lymph node metastasis (p = 1.000), lymphatic invasion (p = 1.000) and blood vessel invasion (p = 0.475), c‐erbB‐2 overexpression of tumor cells (p = 0.616), distant metastasis (p = 0.549), or overall survival (p = 0.759). The local recurrence rate of the two groups was not statistically significant either (16.7% versus 4.3%). However, local recurrence was detected 12% more commonly (p = 0.100), and ~8 months earlier (p = 0.967) in pure IMPC cases, compared to mixed cases. In addition, presence of local recurrence was found to be statistically significantly associated with estrogen receptor (ER) status (p = 0.004), progesterone receptor (PR) status (p = 0.001), and c‐erb‐B2 overexpression (p = 0.016) in all patients. Overall survival rate was significantly associated with ER staining of the tumor (log‐rank = 0.028). Our findings suggest that hormone receptor negativity may explain the more aggressive behavior of pure IMPC compared to mixed cases. Besides, longer survival period of patients with ER positivity, and the relationship of hormone status and c‐erb‐B2 overexpression and local recurrence further support favorable prognostic value of hormone receptors in invasive breast cancer.     

Prognosis of HER2-positive pregnancy-associated breast cancer: Analysis from the French CALG (Cancer Associé à La Grossesse) network

IntroductionThe prevalence of pregnancy-associated breast cancer is increasing. HER2-positive breast cancers typically have a poor prognosis. The objective of our study was to compare the prognosis of patients with HER2-positive breast cancer diagnosed during pregnancy (HER2-positive BCP) to young women diagnosed with HER2-positive breast cancer outside of pregnancy (HER2 non-BCP).MethodsData of patients managed for invasive breast carcinoma between January 2005 and 2020 were retrospectively collected from the database of Tenon University Hospital (Paris, France), part of the “Cancer lié à la Grossesse” network.ResultsFifty-one patients with HER2-positive BCP were matched on age at diagnosis with 51 HER2-positive non-BCP patients. Locally advanced disease with axillary lymph node involvement were frequent. Tumors were frequently aggressive with high grade (p = 0.57) and high Ki67 (p = 0.15). Among the HER2-positive BCP patients, the mean term at diagnosis was 19.3 week of gestation (WG). Eighty-four percent of the patients continued their pregnancy with a mean term at delivery of 34.2WG. Chemotherapy modalities differed between the two groups: neoadjuvant chemotherapy was more frequent in the HER2-positive BCP group (p = 0.03) and adjuvant chemotherapy more frequent in the HER2 non-BCP group (p = 0.009). The recurrence rate was 10% (n = 5) and 18% (n = 9) in the HER2-positive BCP and HER2 non-BCP groups, respectively, p = 0.25. Breast cancer-free survival was poorer in the HER2-positive BCP group with earlier recurrence, p = 0.008. No difference in type of recurrence was found between the groups (p = 0.58).ConclusionThis matched case-control study implies that patients with HER2-positive BCP still have a poorer prognosis than non-pregnant HER-positive patients.     

Comparative Long‐term Study of a Large Series of Patients with Invasive Ductal Carcinoma and Invasive Lobular Carcinoma. Loco‐Regional Recurrence,Metastasis, and Survival

Our aim was to compare histologic and immunohistochemical features, surgical treatment and clinical course, including disease recurrence, distant metastases, and mortality between patients with invasive ductal carcinoma (IDC) or invasive lobular carcinoma (ILC). We included 1,745 patients operated for 1,789 breast tumors, with 1,639 IDC (1,600 patients) and 145 patients with ILC and 150 breast tumors. The median follow‐up was 76 months. ILC was significantly more likely to be associated with a favorable phenotype. Prevalence of contralateral breast cancer was slightly higher for ILC patients than for IDC patients (4.0% versus 3.2%; p = n.s). ILC was more likely multifocal, estrogen receptor positive, Human Epidermal Growth Factor Receptor‐2 (HER2) negative, and with lower proliferative index compared to IDC. Considering conservative surgery, ILC patients required more frequently re‐excision and/or mastectomy. Prevalence of stage IIB and III stages were significantly more frequent in ILC patients than in IDC patients (37.4% versus 25.3%, p = 0.006). Positive nodes were significantly more frequent in the ILC patients (44.6% versus 37.0%, p = 0.04). After adjustment for tumor size and nodal status, frequencies of recurrence/metastasis, disease‐free and specific survival were similar among patients with IDC and patients with ILC. In conclusion, women with ILC do not have worse clinical outcomes than their counterparts with IDC. Management decisions should be based on individual patient and tumor biologic characteristics rather than on lobular versus ductal histology.     

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??Effect of non-sentinel lymph node status on prognosis of Luminal B (HER2 negative) early breast cancer with positive sentinel lymph nodes YE Jing-ming*, XU Ling, LIU Qian, et al. *Breast Disease Center, Peking University First Hospital, Beijing100034, China
Corresponding author: LIU Yin-hua, E-mail??liuyinhua@medmail.com.cn
Abstract Objective To evaluate the effect of non-sentinel lymph node status on prognosis of Luminal B ??HER2 negative?? early breast cancer. Methods Luminal B ??HER2 negative?? early breast cancer with positive sentinel lymph node treated from January 2008 to December 2014 in Peking University First Hospital entered the retrospective study. The clinicopathological features and their relationship with non-sentinel lymph nodes status were analyzed statistically. The effect of non-sentinel lymph nodes status on prognosis of Luminal B ??HER2 negative?? early breast cancer with positive sentinel lymph nodes were also analyzed. Results In the group of 142 patients with positive sentinel lymph nodes ??SLN???? the average number of SLNs detected in each patient were 2.06±1.26. The number of positive SLNs was associated with the status of non-sentinel lymph nodes?? but not the age?? BMI?? menopause?? T stage?? histological grade?? lympho-vascular invasion. Non-SLN axillary lymph node non-metastasis occurred in 78 patients (54.9%), DFS 93%, OS 93.1%; non-SLN axillary lymph node metastasis occurred in 64 patients (45.1%), DFS 95.2%, OS 91.9%. Based on Log-rank (Mantel-Cox) test, There was no significant difference between two groups in DFS (χ2=0.011, P=0.918) and OS (χ2=0.348, P=0.555) . Conclusion The number of positive sentinel lymph nodes in Luminal B ??HER2 negative?? early breast cancer patients with sentinel lymph nodes metastasis were associated with the status of non-sentinel lymph nodes. There were no statistical differences betweennon-sentinel lymph nodes metastasis group and non-metastasis group in disease free survival and over-roll survival.     

The impact of molecular status on survival outcomes for invasive micropapillary carcinoma of the breast

Invasive micropapillary carcinoma (IMPC) is an uncommon variant of breast cancer. Previous studies demonstrated this subtype is often hormone receptor (HR)‐positive, resulting in survival outcomes similar to invasive ductal carcinoma. However, many of these studies were conducted prior to HER2 testing availability. We aim to determine the impact of molecular marker status (including HER2 status) on IMPC survival outcomes. The National Cancer Data Base (NCDB) was used to retrieve patients with biopsy‐proven IMPC from 2007 to 2012. Only patients with known HR and HER2 status were included. Cox multivariate regression was used to determine prognostic factors. In total, 865 patients were included; median follow‐up was 2.5 years. Overall, 651 patients (75.3%) had HR + HER2? disease, 128 (14.8%) had HR + HER2+ disease, 41 (4.7%) had HR‐HER2 + disease, and 45 (5.2%) had triple negative disease. Patients with triple negative disease were more likely to have poorly differentiated histology (66.7%), lymphovascular invasion (73.3%), stage 3 disease (37.8%), undergone mastectomy (68.9%), and positive surgical margins (15.6%). On Cox multivariate regression, those with triple negative disease had worse overall survival (hazard ratio [HR] 7.28, P < 0.001). Other adverse prognostic factors included African‐American descent (HR 2.24, P = 0.018), comorbidity score of 1 (HR 2.50, P = 0.011), comorbidity score ≥2 (HR 3.27, P = 0.06), and ≥3 positive lymph nodes (HR 3.23, P = 0.007). Similar to invasive ductal carcinoma, triple negative disease in IMPC results in worse survival outcomes. This is the largest and first study to characterize molecular status (including HER2 status) in patients with IMPC and its impact on survival outcomes.     

Adenosquamous carcinoma of the breast,an uncommon diagnosis with poor prognosis—Lessons learned from a 12-year analysis of the National Cancer Database

We compared the clinicopathologic characteristics and prognosis of adenosquamous carcinoma (ASQ) of the breast with invasive ductal carcinoma (IDC), utilizing the National Cancer Database (NCDB) from 2004 to 2015. 1 932 688 female patients had invasive breast carcinoma; 1 421 250 had IDC (73.5%); and 453 had ASQ (0.0002%). When compared to IDC, ASQ patients were significantly (P < .05) older and had grade 1 tumors; negative lymph nodes; ER/PR/HER2-negative tumors; and worse 5-year overall survival (64.9% vs 74%, respectively). Our study, largest to date on ASQ, revealed an aggressive carcinoma with a significantly worse prognosis than IDC. “Personalized medicine” treatment approach for patients with this uncommon carcinoma is needed.     

Is There a Role for Oncotype Dx Testing in Invasive Lobular Carcinoma?

Oncotype Dx Breast Cancer Assay is a 21‐gene assay used in estrogen receptor (ER)‐positive breast cancer to predict benefit from chemotherapy (CT). Tumors are placed into one of three risk categories based on their recurrence score (RS). This paper explores the impact of tumor histopathologic features and Oncotype Dx RS on the treatment plan for invasive lobular carcinoma (ILC). Invasive lobular carcinoma cases submitted for Oncotype Dx testing were identified from a clinical data base. The histopathologic and immunohistochemical features and RS subcategory of each tumor, and treatment regimen and medical oncologic assessments of each patient were reviewed. A total of 135 cases of ILC had RS testing, which represented 15% of all ILC diagnosed at the institution over the time period. 80% of ILC was of the classical subtype and all tumors were ER positive and human epidermal growth factor receptor 2 (HER‐2) negative by immunohistochemistry. Sixty three percent of cases were low risk (LR), 35.5% were intermediate risk (IR) and 1.5% were high risk (HR). Both HR cases were pleomorphic ILC. Sixty eight percent of classical ILC had a LR score, while 70% of pleomorphic ILC had an IR score. Patients in the IR category were significantly more likely to undergo CT than patients in the LR category (54% versus 18%; p < 0.0001). In the LR category, those undergoing CT were significantly younger and more likely to have positive lymph nodes (p < 0.05). Qualitative analysis of medical oncologic assessments showed that RS played a role in decision‐making on CT in 74% of cases overall. At our institution, Oncotype Dx RS currently plays a role in the management of a proportion of ILC and impacts on treatment decisions.     

Prognostic impact of HER2-low expression in hormone receptor positive early breast cancer

BackgroundRecent data suggest that human epidermal growth factor receptor 2 (HER2)-low breast cancer may represent a distinct entity. We aimed to compare disease characteristics and outcomes between HER2-low and HER2-0 in estrogen receptor (ER) positive, early-stage breast cancer.MethodsA single center retrospective study comprising all women with ER positive, HER2 negative early breast cancer, for whom an Oncotype DX test was performed between 2005 and 2012. Women were grouped to HER2-low (immunohistochemistry +1 or +2 and in situ hybridization not amplified) or HER2-0. Clinico-pathological features and Oncotype recurrence score (RS) were collected. Data on overall-survival (OS), disease-free survival (DFS) and distant disease-free survival (DDFS) were evaluated according to HER2 expression status.Results608 women were included, of which 304 women had HER2-0 and 304 had HER2-low disease. Lobular subtype was significantly more common in HER-0 compared to HER2-low disease (17% vs. 8%, p = 0.005). The prevalence of other clinic-pathological characteristics and long-term prognosis were comparable between both groups. For women with high genomic risk (RS > 25), HER2-low expression was associated with significantly favorable OS (HR = 0.31, 95% CI 0.11–0.78, p = 0.01), DFS (HR = 0.40, 95% CI 0.20–0.82, p = 0.01) and DDFS (HR = 0.26, 95% CI 0.11–0.63, P = 0.002) compared to women with HER2-0. For women with low genomic risk (RS ≤ 25), long-term prognosis was unrelated to HER2 expression.ConclusionThe prognostic impact of HER2-low expression in early-stage luminal disease varies across the genomic risk, with significant favorable outcomes of HER2-low expression compared to HER2-0 in women with high genomic risk.     

Impact of Her‐2‐Targeted Therapy on Overall Survival in Patients With Her‐2 Positive Metastatic Breast Cancer

Upon disease progression on trastuzumab‐based therapy, patients with HER‐2 positive metastatic breast cancer (MBC) may switch to lapatinib or continue on trastuzumab. We aimed to assess the impact of both strategies on overall survival (OS) in all patients treated for HER‐2 positive MBC at the Medical University Vienna from 1999 until 2009. A total of 201 patients were identified from a breast cancer data base. Of these 115 (57.2%) received multiple lines of trastuzumab‐based therapy, whereas 58 (28.9%) were treated with a single line. A control group of 28 patients (13.9%) had never received trastuzumab as they were treated before 1999, when trastuzumab was registered. OS from diagnosis of metastatic disease was defined as primary study endpoint. Trastuzumab significantly prolonged OS in HER‐2 positive MBC (41 versus 13 months; p < 0.001). Administration of multiple lines further improved OS; this, however, did not reach statistical significance (47 versus 28 months; p = 0.069). Positive estrogen receptor (ER) status (HR 1.6; 95% CI 1.13–2.27) was associated with better outcome compared to negative estrogen receptor status (p = 0.02). Addition of lapatinib did not improve OS significantly in patients with prior trastuzumab‐based therapy (62 versus 47 months; p = n.s.). Patients receiving lapatinib after diagnosis of BM, however, experienced an improvement of OS (22 versus 5 months; p = 0.022). Trastuzumab improves OS in patients with HER‐2 positive MBC with further nonsignificant improvement when administered in multiple lines. Lapatinib did not further improve OS in the entire population; however, lapatinib might improve OS in patients with BM.     

Interferon‐Induced Protein with Tetratricopeptide Repeats 1 (IFIT1) as a Prognostic Marker for Local Control in T1‐2 N0 Breast Cancer Treated with Breast‐Conserving Surgery and Radiation Therapy (BCS + RT)

Interferon‐induced protein with tetratricopeptide repeats 1 (IFIT1) expression, involved in the regulation of translation, has been implicated to mediate resistance to chemotherapy and radiation in cancer cells in vitro. The purpose of this study was to evaluate the prognostic significance of IFIT1 protein expression in patients with breast cancer treated with Breast‐Conserving Surgery and Radiation Therapy (BCS + RT). A tissue microarray was constructed with specimens from 282 women with node‐negative, early‐stage (I/II) breast cancer who were treated with BCS + RT. Immunohistochemistry was used to stain for the IFIT1 protein. Cytoplasmic IFIT1 protein expression levels were correlated with clinicopathologic factors, local relapse‐free survival (LRFS), disease‐free survival (DFS), and overall survival (OS). IFIT1 positivity was found in 123 (49%) of cases. The median follow‐up time was 7.3 years. Eighty percent of the patients had T1 disease, 88% were human epidermal growth factor receptor 2 (HER2) negative, and 20% had triple‐negative breast cancer (TNBC). IFIT1 positivity was associated with estrogen receptor negative status (p = 0.002), progesterone receptor negative status (p = 0.02), TNBC (p = 0.01), and HER2‐positive status (p = 0.006). In univariate and multivariate analysis, IFIT1 positivity was associated with improved LRFS (p = 0.055 and p = 0.04, respectively). Using a log‐rank test, IFIT1 positivity was found to be associated with improved LRFS (94% versus 85%, p = 0.046) but not DFS or OS at 10 years. On subset analysis of the TNBC patients, IFIT1 positivity was found to correlate with improved LRFS (100% versus 53%, p = 0.004) and DFS in (87% versus 49%, p = 0.048) at 10 years. Elevated IFIT1 protein expression is associated with improved LRFS. In addition, our data suggest that IFIT1 expression may help risk stratify patients with TNBC who may benefit from more aggressive therapy. As there is limited data on IFIT1 in breast cancer, additional work is needed to ascertain its significance.     

The St. Gallen surrogate classification for breast cancer subtypes successfully predicts tumor presenting features,nodal involvement,recurrence patterns and disease free survival

AimsTo evaluate how the St. Gallen intrinsic subtype classification for breast cancer surrogates predicts disease features, recurrence patterns and disease free survival.Materials and methodsSubtypes were classified by immunohistochemical staining according to St. Gallen subtypes classification in a 5-tyre system: luminal A, luminal B HER2-neu negative, luminal B HER2-neu positive, HER2-neu non luminal or basal-like. Data were obtained from the records of patients with invasive breast cancer treated at our institution. Recurrence data and site of first recurrence were recorded. The chi(2) test, analysis of variance, and multivariate logistic regression analysis were used to determine associations between surrogates and clinicopathologic variables.ResultsA total of 2.984 tumors were classifiable into surrogate subtypes. Significant differences in age, tumor size, nodal involvement, nuclear grade, multicentric/multifocal disease (MF/MC), lymphovascular invasion, and extensive intraductal component (EIC) were observed among surrogates (p < 0.0001). After adjusting for confounding factors surrogates remained predictive of nodal involvement (luminal B HER2-neu pos. OR = 1.49 p = 0.009, non-luminal HER2-neu pos. OR = 1.61 p = 0.015 and basal-like OR = 0.60, p = 0.002) while HER2-neu positivity remained predictive of EIC (OR = 3.10, p < 0.0001) and MF/MC (OR = 1.45, p = 0.02). Recurrence rates differed among the surrogates and were time-dependent (p = 0.001) and site-specific (p < 0.0001).ConclusionThe St. Gallen 5-tyre surrogate classification for breast cancer subtypes accurately predicts breast cancer presenting features (with emphasis on prediction of nodal involvement), recurrence patterns and disease free survival.     

Prognostic Value of Breast Cancer Subtypes,Ki‐67 Proliferation Index,Age, and Pathologic Tumor Characteristics on Breast Cancer Survival in Caucasian Women

Estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) status are well‐established prognostic markers in breast cancer management. The triple negative breast carcinoma subtype (ER‐/PR‐/HER2‐) has been associated with worse overall prognosis in comparison with other subtypes in study populations consisting of ethnic minorities and young women. We evaluated the prognostic value of breast cancer subtypes, Ki‐67 proliferation index (Ki‐67PI), and pathologic tumor characteristics on breast cancer survival in Caucasian women in our institution, where greater than 90% of the total patient population is white. From 628 new invasive breast cancer cases in our data base (2000‐late 2004), 593 (94%) were identified in Caucasian women. ER/PR/HER2 breast cancer subtypes were classified based on St. Gallen International Expert Consensus recommendations from 2011. ER/PR/HER2 status and its effect on survival were analyzed using a Kaplan–Meier curve. ER/PR/HER2 status, grade, tumor‐node‐metastasis status (TNM)/anatomic stage, and age were analyzed in terms of survival in a multivariate fashion using a Cox regression. Ki‐67PI was analyzed between ER/PR/HER2 groups using the Kruskal–Wallis, Mann–Whitney U‐tests, and 2 × 5 ANOVA. Our results showed that patients with stage IIB through stage IV breast carcinomas were 2.1–16 times more likely to die than patients with stages IA‐B and IIA disease, respectively (95% CI 1.17–3.81 through 9.68–28.03, respectively), irrespective of ER/PR/HER2 subtype. Similar effect was seen with T2, N2/N3, or M1 tumors in comparison with T1, N0/N1, and M0 tumors. Chances of dying increase approximately 5% for every year increase in age. There was a significant main effect of Ki‐67PI between ER/PR/HER2 subtypes, p < .001, but Ki‐67PI could not predict survival. In summary, TNM status/anatomic stage of breast carcinomas and age are predictive of survival in our patient population of Caucasian women, but breast carcinoma subtypes and Ki‐67 proliferation index are not.     

Outcome Following Local‐Regional Recurrence in Women with Early‐Stage Breast Cancer: Impact of Biologic Subtype

Local‐regional recurrence (LRR) after breast‐conserving therapy (BCT) can result in distant metastasis and decreased disease‐free survival (DFS). This study examines factors associated with DFS following LRR. The initial population included 2,233 consecutive women who underwent BCT from 1998 to 2007. Biologic subtype was approximated using a combination of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and tumor grade. Cumulative incidence of DFS after LRR was calculated. The association of clinical, pathologic, and treatment parameters with DFS was evaluated using a Cox regression model. At a median follow‐up of 105 months, 82 patients (3.7%) had a LRR. Of these, 66 (80%) were in‐breast and 16 (20%) involved the ipsilateral lymph nodes. Twenty patients subsequently developed distant metastases. Five‐year DFS after initial recurrence was 69.6% for the overall cohort. On univariate analysis, triple‐negative disease (ER/PR/HER2 negative, TNBC) was associated with reduced DFS (HR = 3.8; 95% CI: 1.8–8.1; p < 0.001). Other factors associated with reduced DFS were larger tumor size (HR = 1.3; 95% CI: 1.03–1.6; p = 0.02), shorter interval from initial diagnosis to LRR (HR = 0.98 per month; 95% CI: 0.97–0.99; p = 0.02), and no salvage surgery (HR = 0.2; 95% CI: 0.09–0.5; p = 0.001). On multivariate analysis, TNBC remained the most significant factor associated with reduced DFS (HR = 4.8; 95% CI: 2.25–10.4; p < 0.001). Compared to women with luminal A disease, those with TNBC had significantly worse DFS (37.5% versus 88.3% at 5 years; p < 0.001). Women with TNBC who developed LRR were at high risk of subsequent recurrence. Efforts should be targeted toward both preventing initial recurrence and decreasing subsequent metastasis.     

Intracystic papillary carcinoma of the breast: A SEER database analysis of implications for therapy

BackgroundIntracystic papillary carcinoma (IPC) of the breast is a rare breast malignancy with an indolent course. However, patients can develop metastatic disease. Indications for surgery and radiotherapeutic management have not been well elucidated.MethodsWe identified 2649 female patients with IPC from the Surveillance, Epidemiology, and End Results (SEER) registry. Differences in demographics, clinical features and survival of patients were assessed using the Kaplan–Meier method and Cox regression.ResultsMedian age was 67 years. The majority of patients were white with Stage 0 disease. Most patients had lymph node evaluation and only 34% received radiation therapy. Using a log-rank test, survival was significantly better in Caucasian compared to African-American patients, patients with early stage disease, negative lymph nodes and those who received radiation (all p < 0.0001). In a Cox regression survival model adjusting for age, stage and grade, patients who were African-American (hazard ratio [HR] 2.0, CI 1.4–2.8; p < 0.0001) had a significantly higher risk of death than Caucasians. Patients who received radiation therapy (HR 0.5, CI 0.3–0.7; p = 0.0003) had a lower chance of death than patients that did not undergo radiation.ConclusionOverall, IPC has a good prognosis. Survival is improved in Caucasian patients and in patients who receive radiation therapy. Radiation therapy should be offered to women with IPC who undergo breast conserving surgery.     

Clinicopathologic analysis of a large series of microinvasive breast cancers

Clinical management of microinvasive breast cancer (Tmic) remains controversial. Although metastases are infrequent in Tmic carcinoma patients, surgical treatment typically includes lymph node sampling. The objective of this study was to determine the rate and predictors of lymph node metastases, recurrence, and survival in a large series of Tmic breast carcinomas. Consecutive cases of Tmic were identified within our health care system from 2001 to 2015. We reviewed results of lymph node sampling and other pathologic factors including hormone receptor/HER2 status, associated in situ tumor size/grade, margin status, number of invasive foci, surgical/adjuvant therapies, and recurrence/survival outcomes. In this cohort, 294 Tmic cases were identified with mean follow‐up of 4.6 years. Of 260 patients who underwent axillary staging, lymph node metastases were identified in 1.5% (all of which were ductal type). All Tmic cases with positive lymph node metastases had associated DCIS with size > 5 cm (5.3‐8.5 cm) compared to a median DCIS tumor size of 2.5 cm (0.2‐19.0 cm) for the entire cohort. No lymph node metastases were seen with microinvasive lobular carcinoma. During the follow‐up period, there were no regional/distant recurrences or breast cancer‐associated deaths in a mean follow‐up period of 4.6 years. Two patients developed subsequent ipsilateral breast cancer (DCIS) in a different quadrant than the original Tmic. Clinical behavior of microinvasive breast cancer in this series is similar to DCIS. Lymph node metastases are uncommon and were only seen with ductal type microinvasive carcinoma. Our data suggest limited benefit for routine node sampling and support management of Tmic similar to DCIS, particularly for patients with DCIS < 5 cm in size.     

Invasive micropapillary carcinoma of the breast in a male patient: Report of a case

INTRODUCTIONWe report a rare case of invasive micropapillary carcinoma in the male breast.PRESENTATION OF CASEA 63-year-old man was referred to our hospital for investigation of a left breast tumor, which could be palpated in the upper lateral quadrant of the left nipple-areola complex. The tumor invaded the areola skin. Ultrasonography showed a 14.8 × 15.0 × 12.4 mm low echoic mass, with an irregular lobulated border. Core needle biopsy indicated invasive ductal carcinoma, but the subtype could not be accurately determined. Mastectomy with axillary lymph node dissection was performed. Pathological examination indicated invasive micropapillary carcinoma, no lymph node metastasis, and a nuclear grade of 2. Immunohistochemical examination showed positive staining for estrogen and progesterone receptors, but negative staining for HER2. The Ki67 index was 5%. Tamoxifen was administered, and recurrence has not been noted for 1 year.DISCUSSIONWomen's IMPC generally shows a high HER2 positivity rate. However, HER2 positivity was noted in only 1 male patient with IMPC (14%) according to our literature review. Furthermore, in all cases of the mixed type that were reviewed, IMPC was associated with papillotubular carcinoma. These findings may be specific to IMPC in male patients.CONCLUSIONIMPC is associated with a high rate of lymph node metastasis or recurrence and advanced vessel invasion, aggressive adjuvant chemotherapy following surgical resection should be selected for patients with IMPC.     

Development and external validation of a nomogram to predict four or more positive nodes in breast cancer patients with one to three positive sentinel lymph nodes

ObjectiveTo develop a nomogram for predicting the possibility of four or more positive nodes in breast cancer patients with 1–3 positive sentinel lymph nodes (SLN).Materials and methodsRetrospective analysis of data of patients from two institutions was conducted. The inclusion criteria were: invasive breast cancer; clinically node negative; received lumpectomy or mastectomy plus SLN biopsy followed by axillary lymph node dissection (ALND); and pathologically confirmed T1-2 tumor, with 1–3 positive SLNs. Patients from one institution formed the training group and patients from the other the validation group. Univariate and multivariate analyses were performed to identify the predictors of four or more positive nodes. These predictors were used to build the nomogram. The area under the receiver operating characteristic curve (AUC) was calculated to assess the accuracy of the model.ResultsOf the 1480 patients (966 patients in the training group, 514 in the validation group), 306 (20.7%) had four or more positive nodes. Multivariate stepwise logistic regression showed number of positive (p < .001) and negative SLN (p < .001), extracapsular extension (p < .001), pT stage (p = .016), and tumor location in outer upper quadrant (p = .031) to be independent predictors of four or more positive nodes. The nomogram was built using these five factors. The AUC was 0.845 in the training group and 0.804 in the validation group.ConclusionThe proposed nomogram appears to accurately estimate the likelihood of four or more positive nodes and could help radiation oncologists to decide on use of regional nodal irradiation (RNI) for breast cancer patients with 1–3 positive nodes but no ALND.     

Tubular carcinoma of the breast: prognosis and response to adjuvant systemic therapy

Background : Tubular carcinoma of the breast is an uncommon and usually small tumour, and is thought to have a favourable prognosis. The present study examined the long‐term prognosis of patients with tubular breast carcinoma and the roles of axillary dissection and adjuvant therapy. Methods : Eighty‐six tubular cases were identified from a large worldwide database of 9520 breast carcinoma patients entered into randomized adjuvant therapy trials run by the International Breast Cancer Study Group from 1978 to 1999. These patients were followed for a median of 12 years. Results : Forty‐two (49%) cases were node‐positive, of which 33 (79%) had 1–3 nodes involved. Ten (32%) of the 31 smaller tumours (≤ 1 cm in size) were node‐positive. Patients with node‐positive tubular carcinoma had a significantly better 10‐year relapse‐free survival (P = 0.006) and survival (P < 0.0001) compared with non‐tubular node‐positive cases. Overall survival was similar for node‐positive and node‐negative tubular carcinoma. Overall, 71 patients (83%) received some form of adjuvant systemic therapy. Of the 86 cases, 43 (50%) received more than one course of chemotherapy. There was an 85% decrease in the risk of death for patients who received more than one course of chemotherapy compared to those who did not (hazard ratio 0.15, 95% confidence interval (CI): 0.03–0.82; P = 0.03). Conclusions : Compared to other histological types of breast cancer, tubular carcinoma has a better long‐term prognosis. Adjuvant chemotherapy may further improve prognosis and involvement of axillary nodes may not be an indicator for early death due to breast carcinoma.