Time to initiation of neo‐adjuvant chemotherapy for breast cancer treatment does not influence patient survival: A study of US breast cancer patients

Delays in the initiation of adjuvant chemotherapy or radiation therapy are associated with worse outcomes in patients undergoing treatment for breast cancer. However, the impact of the time to initiation of neo‐adjuvant chemotherapy (NAC) on patient outcomes has not previously been studied. The purpose of this study was to determine whether delays in NAC initiation impact patient survival. The National Cancer Database was queried for women ≥ 18 years old who underwent NAC within 6 months of being diagnosed with stage I‐III invasive breast cancer in 2010‐2011. ER+ or PR+, Her2? cancers were excluded from analysis. Multivariable Cox proportional hazard modeling was used to evaluate the relationship between time to NAC, sociodemographic, diagnosis, and treatment factors with patient survival. The median age of the 12 806 women included in this study was 52 (range 21‐90) with 62% presenting with cT2 disease and 62% with nodal involvement. Half of the women (50%) had triple negative, 30% ER/PR+Her2+ and 20% ER?PR?Her2+ cancers. The median time to starting NAC was 4 weeks (range 0‐26) for all subtypes. Time to NAC initiation was not associated with a difference in survival for triple negative or Her2+ cancers. Delays from diagnosis to starting NAC are not associated with worse survival for patients with Her2+ or triple negative breast cancer. This study demonstrates that the majority of women in the modern era start NAC in a timely fashion and delays in starting NAC within 6 months of diagnosis do not impact long‐term patient outcomes.     

Predictive value of breast cancer molecular subtypes in Chinese patients with four or more positive nodes after postmastectomy radiotherapy

The molecular subtypes of breast cancer based on status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her2) expression are associated with markedly different clinical outcomes. We retrospectively analyzed 774 breast cancer patients with four or more positive nodes, who underwent mastectomy between March 1999 and December 2007. Treatment with postmastectomy radiotherapy (PMRT) reduced the rates of locoregional recurrence-free survival (LRFS; 6.7% vs. 26.6%), distant metastasis-free survival (DMFS; 26.9% vs. 50.0%), and mortality (24.4% vs. 45.3%) for luminal-A subtypes (ER+ or PR+, Her2-) and reduced LRFS (12.1% vs. 27.5%) for the luminal-B subtype (ER+ or PR+, Her2+) compared with patients not receiving PMRT. However, PMRT did not affect the endpoints for the Her2-enriched or basal subtypes. Thus, understanding the differences in patterns of relapse between the different subtypes of breast cancer may enable targeted adjuvant therapy and improved surveillance decisions.     

经尿道膀胱肿瘤切除术后补救性动脉介入化疗治疗肌层浸润性膀胱癌的疗效分析

目的：探讨补救性髂内动脉化疗存经尿道膀胱肿瘤切除术（transurethralresectionofbladdertumor,TURBT）后证实为肌层浸润性膀胱癌患者中的治疗价值。方法：对34例TURBT患者术后基底部活检及病理结果证实为肌层浸润性的膀胱肿瘤患者行补救性髂内动脉化疗3次。方案为顺铂80mg、表柔吡星50mg、5-氟尿嘧啶1g（或羟基喜树碱30mg）。观察患者肿瘤复发率,Kaplan—Meier法计算总体生存率,肿瘤特异性生存率,无肿瘤复发生存率,并绘制生存曲线。结果：术后经3次补救性髂内动脉化疗及常规膀胱灌注后,29例患者得到保留膀胱（保留膀胱率85．3％）,肿瘤复发13例（肿瘤复发率38．2％）。其中,浅表性复发7例,行TURBT治疗;浸润性复发5例,行全膀胱切除术;骨转移l例,行全身化疗。总体生存率：3年69．78％,5年62．03％。肿瘤特异性生存率：3年77．43％,5年68．83％。无肿瘤复发生存率：1年93．10％,2年70．23％．3年46．82％。结论：补救性动脉介入化疗是TuRBT术后基底部活检及病理结果证实为肌层浸润性的膀胱肿瘤的良好选择。     

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.     

Heterogeneity of Breast Cancer Clinical Characteristics and Outcome in US Black Women—Effect of Place of Birth

Breast cancer mortality in black women is disproportionately high; reasons for this phenomenon are still unclear. In addition to socioeconomic factors, the biology of the tumor may play a role. We analyzed 1,097 incident invasive breast cancer cases diagnosed between 2000 and 2010 in black US women from Long Island and Brooklyn. Thirty‐five percent of women had an estrogen receptor (ER) negative tumor, 46% a progesterone receptor (PR) negative tumor. ER, PR negative tumors were diagnosed at an earlier age (55.8 versus 55.3 years), at a later stage (p = 0.06), were larger in size (p = 0.04), and more frequently treated with neo‐adjuvant chemotherapy (p = 0.06) than ER, PR positive tumors. Determinants of shorter survival were: ER, PR negativity (HR: 2.2, 95% CI: 1.4–3.4), age, and stage at diagnosis (HR: 2.0; 95% CI: 1.5–2.7). ER, PR negative breast cancer born outside of the US experienced a significantly worse survival than ER, PR negative women who were born in the US. ER, PR negative tumors in black women born outside the US, mainly in the Caribbean, are biologically more aggressive than the same size and age‐matched tumors in black women born in the US. Our study suggests that environmental exposures in the country of origin may impact on host cancer interactions and cancer outcome.     

Survival of south african women with breast cancer receiving anti-retroviral therapy for HIV

PurposeBreast cancer outcomes in sub-Saharan Africa is reported to be poor, with an estimated five-year survival of 50% when compared to almost 90% in high-income countries. Although several studies have looked at the effect of HIV in breast cancer survival, the effect of ARTs has not been well elucidated.MethodsAll females newly diagnosed with invasive breast cancer from May 2015–September 2017 at Charlotte Maxeke Johannesburg Academic and Chris Hani Baragwanath Academic Hospital were enrolled. We analysed overall survival and disease-free survival, comparing HIV positive and negative patients. Kaplan-Meier survival curves were generated with p-values calculated using a log-rank test of equality while hazard ratios and their 95% confidence intervals (CIs) were estimated using Cox regression models.ResultsOf 1019 patients enrolled, 22% were HIV positive. The overall survival (95% CI) was 53.5% (50.1–56.7%) with a disease-free survival of 55.8% (52.1–59.3) after 4 years of follow up. HIV infection was associated with worse overall survival (HR (95% CI): 1.50 (1.22–1.85), p < 0.001) and disease-free survival (OR (95% CI):2.63 (1.71–4.03), p < 0.001), especially among those not on ART at the time of breast cancer diagnosis. Advanced stage of the disease and hormone-receptor negative breast cancer subtypes were also associated with poor survival.ConclusionHIV infection was associated with worse overall and disease-free survival. HIV patients on ARTs had favourable overall and disease-free survival and with ARTs now being made accessible to all the outcome of women with HIV and breast cancer is expected to improve.     

Impact of Presurgical Breast Magnetic Resonance Imaging (MRI) on Surgical Planning – A Retrospective Analysis from a Private Radiology Group

Presurgical bilateral breast MRI is being increasingly utilized in newly diagnosed breast cancer patients to identify the presence of other potentially malignant lesions and thereby guide surgical planning. The authors have performed a retrospective analysis of presurgical MRIs in 445 breast cancer patients, consecutively seen in a community practice setting, to determine what risk factors may be associated with bilateral synchronous breast cancer. Clinical, imaging, surgical, and pathological data were collected on these newly diagnosed patients, who underwent presurgical breast MRIs from November 1, 2008 through October 31, 2009. The MRIs detected 84 incremental (additional) malignancies in 66 (14.8%) patients, including 22 patients in the contralateral breast (4.9%) and 48 patients who had ipsilateral incremental malignancies (10.8%). The presurgical breast MRIs had a sensitivity of 99% and a specificity of 86%. Based on the imaging study and the subsequent biopsy(s), 105 patients (23.6%) had changes in their surgical planning. For those with incremental breast malignancies, the synchronous bilateral breast cancer patients were older (67.5 ± 13.5 years, p = 0.01). Patients with ipsilateral incremental malignancies were younger (55.6 ± 10.4 years of age, p = 0.03). A strong family history and ductal carcinoma in situ (DCIS) as the index lesion also appeared to be associated with increased bilateral malignancy detection. The authors conclude that although presurgical MRI remains controversial, our data support its role in surgical planning for newly diagnosed breast cancer patients.     

Association between contralateral background parenchymal enhancement on MRI and outcome in patients with unilateral invasive breast cancer receiving neoadjuvant chemotherapy

PurposeThe purpose of this study was to retrospectively investigate whether background parenchymal enhancement (BPE) of the contralateral breast on magnetic resonance imaging (MRI) is associated with clinical outcomes in patients with unilateral invasive breast cancer receiving neoadjuvant chemotherapy (NAC).Materials and methodsA total of 228 women (47.6 years ± 10 [SD]; range: 24–74 years) with invasive breast cancer who underwent NAC between 2005 and 2013 were included. All included patients underwent breast MRI before and after NAC. Quantitative semiautomated analysis of BPE of the contralateral healthy breast was performed. The enhancement level on baseline MRI (baseline BPE) and on MRI after chemotherapy (final BPE) and the change in enhancement rate between baseline MRI and final MRI were recorded. Cox regression was used to test associations between BPE variables, patient and tumor characteristics, overall survival (OS) and disease–free survival (DFS). Subgroup analyses based on menopausal status and immunohistochemical subtypes were performed.ResultsMedian follow-up was 92 months. Multivariable analysis revealed that Ki-67 level (P = 0.026) and receipt of mastectomy (P = 0.015) were independent variables associated with OS while Ki-67 level (P = 0.010) and post-NAC pathological node categorization (P = 0.027) were independent variables associated with DFS. BPE was not associated with OS (P = 0.500, 0.546 and 0.712 for baseline BPE, final BPE and BPE change, respectively) or with DFS (P = 0.568, 0.412 and 0.327, respectively).ConclusionBPE of the contralateral breast on MRI may have limited prognostic value in patients with breast cancer treated with NAC.     

Flat epithelial atypia on core needle biopsy does not always mandate excisional biopsy

Flat Epithelia Atypia (FEA) is a proliferative lesion of the breast where cells demonstrate columnar change and cytologic atypia. This lesion has been identified as distinct from the classic atypical hyperplasias (AH). While many patients undergo excisional biopsy, management of FEA identified on core needle biopsy (CNB) is controversial, and the rate of associated ductal carcinoma in situ (DCIS) or invasive cancer is not well defined. The aim of this study was to determine the upstage rate of FEA diagnosed by CNB. We identified patients from a prospectively maintained data base who had FEA diagnosed by CNB from 01/2010 to 07/2015. Patient variables collected included age at presentation, imaging findings, pathologic findings following surgical excision, and subsequent development of breast cancer. Of 132 patients, 62 (n = 62/132, 47.0%) patients had FEA associated with DCIS and invasive ductal carcinoma (IDC) on CNB and were excluded from analysis. Of the remaining 70 patients, median age was 52 (range 31‐84) years. Thirty‐two (45.7%) patients had FEA plus AH, 4 (5.7%) patients had FEA plus lobular carcinoma in situ (LCIS), and 34 (48.6%) patients had FEA alone or with another non‐pathologic finding (pure FEA). Two (6.3%) patients with FEA plus AH had DCIS or IDC on subsequent excisional biopsy. Of the 34 patients with pure FEA who underwent excisional biopsy, only one (2.9%) was found to have IDC. Twenty‐two (64.7%) patients with pure FEA who underwent excisional biopsy presented with calcifications on mammography. None of these patients had cancer on excisional biopsy, and 10 (45.5%) patients had AH (3 ADH, 3 ALH, and 4 both ALH and ADH). Twelve (n = 12/34, 35.3%) patients with pure FEA underwent CNB for a mass or asymmetry noted on imaging. Of these 12 patients, 9 (75.0%) had benign findings on excisional biopsy, two (16.7%) patients had AH, and one (8.3%) patient had IDC. Median follow‐up was 4.6 years (IQR 3.1‐6.5 years). Three (4.3%) patients subsequently developed IDC, two of which were in the contralateral breast. FEA is often found in combination with ADH and ALH as well as carcinoma on CNB. In our study, pure FEA was upstaged to cancer in only 2.9% of patients. Mammographic findings unlikely predict upstaging to malignancy. These findings suggest that excisional biopsy may not be warranted in patients with pure FEA and could be managed with close imaging surveillance.     

Breast Cancer Subtypes as Defined by the Estrogen Receptor (ER), Progesterone Receptor (PR), and the Human Epidermal Growth Factor Receptor 2 (HER2) among Women with Invasive Breast Cancer in California, 1999–2004

Abstract: Breast cancer research examining either molecular profiles or biomarker subtypes has focused on the estrogen receptor negative/progesterone receptor negative/human epidermal growth factor receptor 2 negative (ER−/PR−/HER2−) and ER−/PR−/HER2+ subtypes. Less is known about the epidemiology or clinical outcome of the other subtypes. This study examines the eight combinations of ER/PR/HER2 in patients with invasive breast cancer. The 5‐year relative survival and the distribution among demographic, socioeconomic, and tumor characteristics of each of the subtypes are examined. Using the California Cancer Registry, 61,309 women with primary invasive breast cancer were classified according to ER/PR/HER2 status. Five‐year relative survival was computed for the eight subtypes. Bivariate analyses were used to assess the distribution of cases across all subtypes. Multivariate logistic regression was used to compute the adjusted odds of having one of the five subtypes with the best and worst survival. Survival varied from 96% (ER+/PR+/HER2−) to 76% (ER−/PR−/HER2+ and ER−/PR−/HER2−). The four subtypes with the poorest survival were all ER negative. Women who were younger than age 50, non‐Hispanic black or Hispanic, of the lowest SES groups, and had stage IV tumors that were undifferentiated were overrepresented in ER−/PR−/HER2+ and triple negative (ER−/PR−/HER2−) subtypes. Asian Pacific Islanders had increased odds (OR = 1.41; 95% confidence interval [CI] = 1.26–1.57) of having the ER−/PR−/HER2+ subtype. Stage III tumors (OR = 1.25; 95% CI = 1.08–1.44) and stage IV tumors (OR = 1.58; 95% CI = 1.27–1.98) had higher odds than stage I tumors of being ER−/PR−/HER2+. Stage IV tumors (OR = 0.54; 95% CI = 0.44–0.67) strongly decreased the odds of the ER−/PR−/HER2− subtype. Poorly differentiated and undifferentiated tumors were over 20 times as likely as well‐differentiated tumors of being ER−/PR−/HER2− or ER−/PR−/HER2+. There are considerable differences in survival, demographics, and tumor characteristics among the eight subtypes. We recommend reporting breast cancer as an ER/PR/HER2 subtype and precisely documenting demographic and tumor characteristics.     

Extracellular Matrix 1 (ECM1) Expression Is a Novel Prognostic Marker for Poor Long-Term Survival in Breast Cancer: A Hospital-Based Cohort Study in Iowa

Introduction  Previous work in a small, unselected series showed that up to 83% of breast carcinomas overexpress ECM1 by immunohistochemistry (IHC) and that tumors with lymph node metastases are more likely to be ECM1-positive. We sought to further evaluate ECM1 expression and its effect on prognosis in an unselected cohort of patients with breast cancer. Methods   ECM1 expression was examined by IHC in 134 women diagnosed with invasive breast cancer between 1986 and 1989 and correlated with clinical parameters and outcomes, including disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS) using Cox proportional hazards regression. Results  During follow-up, 83 of 134 (66%) patients died. The median follow-up was 211 (range, 183–245) months for surviving patients. Based on a previously described cutoff of 10% staining, 47% of breast cancers were ECM1-positive. ECM1-positive tumors were associated with increasing patient age (P = 0.01). In multivariate analyses, while controlling for age, ER status, tumor grade, stage, and treatment, ECM1 expression emerged as a significant predictor of DSS (hazard ratios, 4.16 (P = 0.009) and 11.6 (P = 0.01) at 10 and 15 years, respectively) and DFS (hazard ratio, 3.08 (P = 0.03) at 15 years) with ECM1 overexpression predicting poorer survival. Conclusions   ECM1 was overexpressed in approximately half of invasive breast carcinomas and is an important prognostic marker, particularly for predicting poorer DSS, with its predictive value increasing with time from diagnosis. Further work is needed to confirm these findings and determine whether ECM1 expression is predictive of response to specific therapy.     

Radiation therapy utilization and outcomes for older women with breast cancer: Impact of molecular subtype and tumor grade

BackgroundRadiation therapy (RT) utilization for elderly women with respect to human epidermal growth factor receptor 2 (HER2) receptor status has not been evaluated. Our purpose was to determine differences in RT utilization and breast cancer specific survival (BCSS) for elderly breast cancer patients with distinct molecular biomarkers.MethodsThe Surveillance, Epidemiology, and End Results database was queried for women ≥70 years of age diagnosed with T1N0M0 breast cancer between 2010 and 2013 receiving breast conservation. Chi-squared analysis was performed to determine the difference in RT utilization between groups. Multivariable logistic regression analysis was performed to determine predictors for RT use. Kaplan-Meier curves were created and the log-rank test done to compare differences in breast cancer specific survival (BCSS) between groups.ResultsA total of 12,312 patients met the inclusion criteria. Receipt of RT for patients with distinct tumor biomarkers was as follows: 55.7% for patients with Estrogen Receptor (ER) +/HER2+; 57.1% for patients with ER+/HER2-; 65.6% for patients with ER-/HER2+; and 69.2% for ER-/HER2- patients (p < 0.001). Factors associated with RT use included ER-/HER2- status, 70–74 years of age, and high grade disease, while adjuvant RT was associated with improve BCSS in ER+/HER2- and ER-/HER2- patients.ConclusionsPatients 70–74 years old and those with ER-/HER2- are more likely to receive adjuvant RT. Moreover, adjuvant RT is associated with improvements in BCSS in ER+/HER2- and ER-/HER2- patients. Given possible poor compliance with hormonal therapy, the omission of RT in ER + patients, without consideration of HER2 status, should be undertaken with care.     

Preoperative assessment of breast cancer: Multireader comparison of contrast-enhanced MRI versus the combination of unenhanced MRI and digital breast tomosynthesis

PurposeTo compare the sensitivity for breast cancer (BC) and BC size estimation of preoperative contrast-enhanced magnetic resonance imaging (CEMRI) versus combined unenhanced magnetic resonance imaging (UMRI) and digital breast tomosynthesis (DBT).Patients and methodsWe retrospectively included 56 women who underwent DBT and preoperative 1.5 T CEMRI between January 2016–February 2017. Three readers with 2–10 years of experience in CEMRI and DBT, blinded to pathology, independently reviewed CEMRI (diffusion-weighted imaging [DWI], T2-weighted imaging, pre- and post-contrast T1-weighted imaging) and a combination of UMRI (DWI and pre-contrast T1-weighted imaging) and DBT. We calculated per-lesion sensitivity of CEMRI and UMRI + DBT, and the agreement between CEMRI, UMRI and DBT versus pathology in assessing cancer size (Bland-Altman analysis). Logistic regression was performed to assess features predictive of cancer missing.ResultsWe included 70 lesions (64% invasive BC, 36% ductal carcinoma in situ or invasive BC with in situ component). UMRI + DBT showed lower sensitivity (86–89%) than CEMRI (94–100%), with a significant difference for the most experienced reader only (p = 0.008). False-positives were fewer with UMRI + DBT (4–5) than with CEMRI (18–25), regardless of the reader (p = 0.001–0.005). For lesion size, UMRI showed closer limits of agreement with pathology than CEMRI or DBT. Cancer size ≤1 cm was the only independent predictor for cancer missing for both imaging strategies (Odds ratio 8.62 for CEMRI and 19.16 for UMRI + DBT).ConclusionsUMRI + DBT showed comparable sensitivity and less false-positives than CEMRI in the preoperative assessment of BC. UMRI was the most accurate tool to assess cancer size.     

Pathologic complete response after neoadjuvant chemotherapy in HER2-overexpressing breast cancer according to hormonal receptor status

ObjectiveFor patients with HER2-positive breast cancer, the prognostic impact of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) is unclear when stratified by hormonal receptor (HR) status; however, the impact of pCR on survival when stratified by hormonal receptor (HR) status is uncertain.Patients and methodsThis multicenter retrospective study investigated the predictors of pCR and its prognostic value in Japanese patients 366 HER2-positive breast cancer who received NAC. pCR was defined as no invasive residual tumor in the breast or axilla.ResultsMedian follow-up was 55 months. Multivariate analysis revealed that HR status (OR, 0.37; p < 0.001) was one of the independent predictors of pCR. Five-year recurrence-free survival was higher in HR-negative patients with pCR (93%) than in those without pCR (68%), and pCR was independently prognostic (hazard ratio, 0.32; p = 0.005). However, 5-year recurrence-free survival was not different between HR-positive patients with pCR (94%) and those without pCR (84%), and pCR was not significantly prognostic (hazard ratio, 0.53; p = 0.39). In addition, 5-year overall survivals were high and similar (97% in pCR, 94% in non-pCR). Among 204 patients treated with neoadjuvant trastuzumab, pCR was not significantly prognostic in the HR-positive group (hazard ratio, 0.63; p = 0.56).ConclusionOur study suggested that the HER2-positive HR-positive patients had a good prognosis despite the lower achievement rate of pCR, whose prognostic impact was smaller than that in the HER2-positive HR-negative patients. The treatment strategy for HER2-positive breast cancer can be stratified by HR status.     

Is the TNM Staging System for Breast Cancer Still Relevant in the Era of Biomarkers and Emerging Personalized Medicine for Breast Cancer – An Institution's 10‐year Experience

We have previously demonstrated that TNM status and age were significant predictors of overall survival (OS) in our study population of Caucasian patients with invasive breast carcinoma (2000–2004 study period). However, estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) biomarker expression was not predictive of OS when using the five‐group ER/PR/HER2 subtype classification system recommended by St. Gallen International Consensus Panel in 2011. The current study reassessed the relevance of tumor biomarkers (ER/PR/HER2) in our study population using a recently proposed biologic TNM (bTNM) classification system in which the inclusion of triple negative ER/PR/HER2 phenotype (TNP) could improve the prognostic accuracy of TNM for staging, prognosis and treatment of breast cancer patients. Seven hundred eighty‐two Caucasian women diagnosed with invasive ductal carcinoma from 1998 to 2008 were grouped according to their TNM stage and TNP versus non‐TNP ER/PR/HER2 phenotype. OS was measured comparing these categories using Kaplan Meier curves and Cox regression analysis. TNM stage (Stage II = HR 1.41, 95% CI 1.01–1.97; Stage III = HR 3.96, 95% CI 2.68–5.88; Stage IV = HR 27.25, 95% CI 16.84–44.08), and age (HR 1.05, 95% CI 1.04–1.06) were significant predictors of OS. TNP significantly worsened prognosis/survival only in higher TNM stages (Stage III = HR 3.08, 95% CI 1.88–5.04, Stage IV = HR 24.36, 95% CI 13.81–42.99), but not in lower stages (I and II). Our data support the traditional TNM staging as a continued relevant predictive tool for breast cancer outcomes and show that biomarkers primarily improve the accuracy of TNM staging in advanced stages of breast cancer. We suspect that type of ER/PR/HER2 classification system(s) (St. Gallen, TNP, etc.), characteristics of populations studied (Caucasians, minorities, etc.), and the time period chosen for a study are major factors that determine impact of biomarkers on the prognostic accuracy of TNM. We propose systematic analyses of these factors before biomarkers are fully incorporated into the TNM staging system (bTNM).     

Role of cervical ultrasound in detecting thyroid pathology in primary hyperparathyroidism

Background

Minimally invasive parathyroidectomy for primary hyperparathyroidism is made possible with accurate preoperative imaging. In addition to the detection of parathyroid adenomas, cervical ultrasound also provides concomitant assessment of the thyroid gland, and many surgeons believe that it is essential. However, the incidental identification of thyroid nodules may then subject patients to further workup and potentially invasive thyroid procedures. We sought to determine the long-term consequence of omitting preoperative ultrasound on the development of thyroid pathology and cancer.

Methods

At our institution, 222 patients with primary hyperparathyroidism underwent parathyroidectomy without preoperative cervical ultrasound from 1990–2001. Thyroid pathology discovered by follow-up after parathyroidectomy, subsequent biopsy, and surgical interventions were analyzed.

Results

Of the 222 patients who underwent parathyroidectomy, the mean age was 55 ± 1 y and 149 were female (67%). In the course of their follow-up after parathyroidectomy, 13 patients (6%) received a cervical ultrasound, and seven of 13 (3%) underwent fine needle aspiration of a thyroid nodule. Only one of seven (0.4% of all patients) was ultimately diagnosed with thyroid cancer. Four additional patients were discovered to have thyroid malignancies as a result of intraoperative decision making. All five patients are currently alive with an average follow-up time of 14.9 ± 1.6 y. No patients in this series had an unnecessary thyroid intervention.

Conclusions

In patients who underwent parathyroidectomy without a preoperative ultrasound, only a small number (0.4%) were subsequently diagnosed with thyroid cancer. Furthermore, omission of ultrasound during the localization of parathyroid glands does not have a negative impact on the diagnosis of thyroid pathology as all patients who had thyroid cancer had good outcomes, and in fact, may prevent unnecessary thyroid interventions. Therefore, the use of cervical ultrasound for parathyroid localization should be considered optional rather than essential.     

Treatment and survival outcome for molecular breast cancer subtypes in black women

OBJECTIVE: To analyze whether the local-regional surgical treatments (breast-conserving therapy, mastectomy) resulted in different overall survival, distant metastasis-free survival, and locoregional recurrence-free survival rates for the various molecular breast cancer subtypes. SUMMARY BACKGROUND DATA: Molecular gene expression profiling has been proposed as a new classification and prognostication system for breast cancer. Current recommendation for local-regional treatment of breast cancer is based on traditional clinicopathologic variables. METHODS: Retrospective analysis of 372 breast cancer cases with assessable immunohistochemical data for ER, PR, and Her-2/neu receptor status, diagnosed from 1998 to 2005. Molecular subtypes analyzed were luminal A, luminal B, basal like, and Her-2/neu. RESULTS: No substantial difference was noted in overall survival, and locoregional recurrence rate between the local-regional treatment modalities as a function of the molecular breast cancer subtypes. The basal cell-like subtype was an independent predictor of a poorer overall survival (hazard ratio [HR] = 2.52, 95% confidence interval [CI] 1.28-4.97, P < 0.01) and a shorter distant metastasis-free survival time (HR = 3.61, 95% CI 1.27-10.2, P < 0.01), and showed a tendency toward statistical significance as an independent predictor of locoregional recurrence (HR = 3.57, 95% CI 0.93-13.6, P = 0.06). CONCLUSIONS: The basal cell-like subtype is associated with a worse prognosis, a higher incidence of distant metastasis, and may be more prone to local recurrence when managed with breast-conserving therapy.     

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.     

Contemporary management of breast cancer during pregnancy and subsequent lactation in a multicenter cohort of young women with breast cancer

The incidence of breast cancer diagnosed during pregnancy is increasing. We sought to characterize patient, treatment, pregnancy and lactation factors among young women with newly diagnosed breast cancer during pregnancy in a prospective cohort study. We identified all women who were pregnant when diagnosed with invasive breast cancer among those enrolled in the Young Women's Breast Cancer Study (NCT01468246), and collected details on pregnancy, birth and lactation from surveys, and treatment information medical record review. Of 1302 enrolled participants, 976 women with invasive breast cancer completed full baseline surveys, among whom 39 (4.0%) patients reported being pregnant at diagnosis. Median age at diagnosis was 34 years (range: 25‐40), with stage distribution: I, 28%; II, 44%; III, 23%; and IV, 5%. 74% of patients (29/39) had grade 3 tumors, 59% (23/39) ER‐positive, and 31% (12/39) HER2‐positive disease. 23 (59%) had surgery during pregnancy, 4 (17%) during the first trimester. Among the women who had surgery during pregnancy, 61% (14/23) underwent lumpectomy, 35% (8/23) unilateral, and 4% (1/23) bilateral mastectomy. All patients who had chemotherapy (51%, 20/39) received it in second and third trimesters, and had ACx4. There were 31 live births, 2 spontaneous, and 5 therapeutic abortions. Among live births, 16 (41%) were before 37 weeks of gestation. Three women reported breastfeeding. Within 6 months after delivery, comprehensive staging in 13 patients showed upstaging in four patients. In a contemporary cohort of young women with breast cancer, pregnancy at diagnosis is relatively uncommon. Treatment during pregnancy can generally be consistent with standard surgical and chemotherapy approaches, with attention to timing of therapies. Longer‐term outcomes including effects of some timing issues including delayed use of anti‐HER2 therapy on patient outcomes warrant further research.