Gestational Age and the Risk of Maternal Breast Cancer: A Population‐Based Case–Control Study

There is limited evidence that the gestational age at delivery may influence the risk of maternal breast cancer. While extreme prematurity has been suggested to increase the risk, there seems to be no study available so far that investigates the due effects of a late delivery. This research aimed to identify the impact of both preterm and late deliveries on the risk of maternal breast cancer within a period of 5 years after birth. Our dataset was created by linking data from the Nevada Cancer Registry database (1995–2008) and the birth certificates issued by the Nevada State Health Division (1994–2003). The study cohort consisted of 213,250 women who gave birth from January 1, 1994 to December 31, 2003. We performed a nested population‐based case – control study on 126 Nevada mothers with a first lifetime breast cancer diagnosed from January 1, 1995 through December 31, 2003, and 504 Nevada cancer‐free mothers. Women with pregnancies who progressed beyond 40 weeks of gestation were at a significantly lower risk of developing breast cancer for the 5‐year period following a delivery, when compared to women who delivered at 37–40 weeks of gestation (OR: 0.33, 95% CI: 0.11–0.92) in a multivariate model. Additional pregnancy characteristics did not significantly predict the risk of maternal breast cancer. Pregnancies that extended beyond 40 weeks of gestation were strongly associated with a lower likelihood of premenopausal breast cancer. Biological plausibility for this association may correspond to the fact that as pregnancy develops into more advanced stages, mammary cells have more time to attain complete differentiation and maturation; a process that starts early in the third trimester.     

Impact of Surgery on Survival in Stage IV Breast Cancer

We aimed to assess retrospectively the survival outcome in patients with stage IV breast cancer who underwent surgery. In a retrospective, nonrandomized study of stage IV breast cancer patients diagnosed in a single institution between 2000 and 2012, we assessed patient's survival in the context of baseline characteristics. A total 678 patients with metastatic breast cancer were included; 412 (60.77%) underwent surgery for the primary tumor (Surgery group), and 266 (39%) did not underwent surgery for the primary tumor (Nonsurgery group), with a median follow‐up of 41 months. Patients in the Surgery group had longer survival (41 versus 27 months, p < 0.0029). The 5‐year survival rate for Surgery group was 34% compared with 14% for the Nonsurgery group. A multivariate analysis revealed surgery (p = 0.0003), large tumor size (p = 0.0195), ER‐positive (p < 0.0001), and metastasis at presentation (p = 0.0032) were prognostic variables. Loco‐regional surgery does confer a survival advantage in stage IV breast cancer, however, selection bias cannot be excluded, a well‐designed and powerful randomized, controlled trial would be valuable to answer whether surgery can improve survival.     

Trastuzumab Beyond Progression for HER2 Positive Metastatic Breast Cancer: Progression‐Free Survival on First‐Line Therapy Predicts Overall Survival Impact

Trastuzumab beyond first progression in the metastatic setting has been adopted based on limited data suggesting improved outcomes compared to second‐line chemotherapy alone although predictive factors for preferential benefit remain elusive. We conducted a retrospective review of all patients receiving trastuzumab for HER2 + metastatic disease between Jan 1, 1999–June 15, 2011. Univariate and time to event analyses described treatment and survival patterns. Median duration of each line of therapy and overall survival times for covariates, including treatment era (pre versus post Jan 1, 2005), lines of trastuzumab‐based therapy (1 versus 2 versus 3 + ), first‐line chemotherapy partner (docetaxel/paclitaxel versus other) and median exposure to first‐line trastuzumab‐based therapy (=/> versus < cohort median) were estimated. A total of 119 patients received a median of two lines of trastuzumab‐based therapy (range 1–8). Median overall survival was 21.8 months (95% CI = 14.5–27.1 m), by era was 15.6 m (95% CI = 9.7–24.8 m) versus 26.1 m (95% CI = 20.0–39.3 m; p = 0.11) and by lines of trastuzumab‐based therapy received was 10.6 m (95% CI = 5.3–17.4 m) versus 13.9 m (95% CI = 9.5–27.6 m) versus 32.5 m (95% CI = 25–49.4 m) (p = 0.0014). Median overall survival was significantly longer for those receiving taxanes with trastuzumab compared to other first line partners (26.1 m, 95% CI = 17.8–31.4 m versus 14.5 m, 95% CI = 9.4–21.9 m, p = 0.02). Median overall survival with duration of first‐line trastuzumab‐based therapy =/> cohort median was 31.9 m (95% CI = 26.2–52.2 m) versus 10.3 m for shorter durations (95% CI = 6.9–15.6 m; p < 0.0001). Our observations support progression‐free survival on first‐line trastuzumab‐based therapy as a clinically relevant predictive factor for overall survival benefit with the adoption of a trastuzumab beyond progression treatment strategy.     

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.     

Prognostic Value of PD‐L1 in Breast Cancer: A Meta‐Analysis

Programmed cell death 1 ligand 1 (PD‐L1) is a promising therapeutic target for cancer immunotherapy. However, the correlation between PD‐L1 and breast cancer survival remains unclear. Here, we present the first meta‐analysis to investigate the prognostic value of PD‐L1 in breast cancer. We searched Pubmed, Embase, and Cochrane Central Register of Controlled Trials databases for relevant studies evaluating PD‐L1 expression and breast cancer survival. Fixed‐ and random‐effect meta‐analyses were conducted based on heterogeneity of included studies. Publication bias was evaluated by funnel plot and Begg's test. Overall, nine relevant studies with 8583 patients were included. PD‐L1 overexpression was found in 25.8% of breast cancer patients. PD‐L1 (+) associated with several high‐risk prognostic indicators, such as ductal cancer (p = 0.037), high tumor grade (p = 0.000), ER negativity (p = 0.000), PR negativity (p = 0.000), HER2 positivity (p = 0.001) and aggressive molecular subtypes (HER2‐rich and Basal‐like p = 0.000). PD‐L1 overexpression had no significant impact on metastasis‐free survival (HR 0.924, 95% CI = 0.747–1.141, p = 0.462), disease‐free survival (HR 1.122, 95% CI = 0.878–1.434, p = 0.357) and overall specific survival (HR 0.837, 95% CI = 0.640–1.093, p = 0.191), but significantly correlated with shortened overall survival (HR 1.573, 95% CI = 1.010–2.451, p = 0.045). PD‐L1 overexpression in breast cancer associates with multiple clinicopathological parameters that indicated poor outcome, and may increase the risk for mortality. Further standardization of PD‐L1 assessment assay and well‐controlled clinical trials are warranted to clarify its prognostic and therapeutic value.     

Primary tumor resection in metastatic breast cancer: A propensity‐matched analysis, 1988‐2011 SEER data base

Primary tumor resection (PTR) in metastatic breast cancer is not a standard treatment modality, and its impact on survival is conflicting. The primary objective of this study was to analyze impact of PTR on survival in metastatic patients with breast cancer. A retrospective study of metastatic patients with breast cancer was conducted using the 1988‐2011 Surveillance, Epidemiology, and End Results (SEER) data base. Cox proportional hazards regression models were used to evaluate the relationship between PTR and survival and to adjust for the heterogeneity between the groups, and a propensity score‐matched analysis was also performed. A total of 29 916 patients with metastatic breast cancer were included in the study, and 15 129 (51%) of patients underwent primary tumor resection, and 14 787 (49%) patients did not undergo surgery. Overall, decreasing trend in PTR for metastatic breast cancer in last decades was noted. Primary tumor resection was associated with a longer median OS (34 vs 18 months). In a propensity score‐matched analysis, prognosis was also more favorable in the resected group (P = .0017). Primary tumor resection in metastatic breast cancer was associated with survival improvement, and the improvement persisted in propensity‐matched analysis.     

Recruitment of a Population‐Based Sample of Young Black Women with Breast Cancer through a State Cancer Registry

Given that Black women remain underrepresented in clinical research studies, we sought to recruit a population‐based sample of young Black women with breast cancer through a state cancer registry. Demographic and clinical information on all Black women diagnosed with invasive breast cancer at or below age 50 between 2009 and 2012 in Florida was obtained through the state cancer registry. Survivors were invited to participate in the study through state‐mandated recruitment methods. Participant demographic and clinical characteristics were compared using Chi‐squared tests for categorical variables and the two sample t‐test for continuous variables to identify differences between: (i) consented participants versus all other eligible; and (ii) living versus deceased. Of the 1,647 young Black women with breast cancer, mean age at diagnosis was 42.5, with the majority having localized or regional disease, unmarried, privately insured, and employed. There were no significant differences in demographic and clinical variables between the 456 consented study participants versus the remaining 1,191 presumed eligible individuals. Compared to potential participants, women determined to be deceased prior to recruitment (n = 182) were significantly more likely to have distant disease and a triple‐negative phenotype. They were also significantly more likely to be unemployed, and uninsured or have public insurance (i.e., Medicaid or Medicare). Our results demonstrate that recruitment of a population‐based sample of breast cancer survivors through a state cancer registry is a feasible strategy in this underserved and underrepresented population. However, survival bias, which was observed due to the lag time between diagnosis and recruitment, is important to adjust for when generalizing findings to all young Black breast cancer patients.     

Prognostic Significance of Survivin in Breast Cancer: Meta‐analysis

Survivin, an inhibitor of apoptosis protein, is a potentially prognostic factor and therapeutic target in breast carcinoma, but no consensus exists based on heterogeneous data. The aim of this present study is to clarify the prognostic relevance of survivin in breast cancer patients. Relevant articles were screened in PubMed and EMBASE databases. Patients’ clinical characteristics, overall survival (OS), disease/recurrence‐free survival (DFS/RFS) and positive expressed survivin rates were extracted for further analysis. Statistics extracted from Kaplan–Meier survival curves were calculated indirectly with methods developed by Parmar, Williamson, and Tierney. Multivariate Cox hazard regression analysis data were used directly in Stata 11.0. Pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated to evaluate the prognostic role of survivin in breast cancer. Online literature search identified 23 articles containing 3,259 breast cancer patients. Our meta‐analysis of all included studies about survival outcomes showed positive correlation between poor prognosis and survivin expression. Pooled HRs (95% CIs) for OS and DFS/RFS were 1.37 (1.12–1.68) and 1.34 (1.02–1.76), respectively. Subgroup analyses considering methods used to detect survivin (immunohistochemistry or not) and localization of survivin (whole, nuclear or cytoplasm of the cell) were also conducted, and all the above analyses supported the stability of the prognostic role of survivin. In addition, our study revealed a significant association between survivin expression and lymph node metastasis (OR: 2.74; 95% CI: 1.27–5.93) or stage of breast cancer (OR: 2.01; 95% CI: 1.29–3.13). Positive expression of survivin demonstrated a significantly higher risk of recurrence and decreased OS rates in breast cancer.     

Factors Affecting Distant Disease-Free Survival for Primary Invasive Breast Cancer: Use of a Log-Normal Survival Model

Background: Invasive breast cancer is a frequently diagnosed disease that now comes with an ever expanding array of therapeutic management options. We assessed the effects of 20 prognostic factors in a multivariate context.Methods: We accrued clinical data for 156 consecutive patients with stage 1–3 primary invasive breast cancer who were diagnosed in 1989–1990 at the Henrietta Banting Breast Center, and followed to 1995. There is complete follow-up for 91% of patients (median follow-up of 4.9 years). The event of interest was distant recurrence (for distant disease-free survival, DFS). We used Cox and log-normal step-wise regression to assess the multivariate effects of the following factors on DFS: age, tumor size, nodal status, histology, tumor and nuclear grade, lymphovascular and perineural invasion (LVPI), ductal carcinoma-in-situ (DCIS) type, DCIS extent, DCIS at edge of tumor, ER and PgR, ERICA, adjuvant systemic therapy, ki67, S-phase, DNA index, neu oncogene, and pRb.Results: There was strong evidence against the Cox assumption of proportional hazards for nodal status, and nodal status was not in the Cox step-wise model. With step-wise log-normal regression, a large tumor size (P < .001), positive nodes (P 5 .002), high nuclear grade (P 5 .01), presence of LVPI (P 5 .03), and infiltrating duct carcinoma not otherwise specified (P 5 .05) were associated with a reduction in DFS.Conclusions: For nodal status, there was strong evidence against the Cox assumption of proportional hazards, and it was not included in the Cox model although it was in the log-normal model. Only traditional factors were included in the step-wise models. Thus, this statistical management of prognostic markers in breast cancer appears to be very important.     

Potential of Reduction in Total Tumor Volume Measured with 3D‐MRI as a Prognostic Factor for Locally‐Advanced Breast Cancer Patients Treated with Primary Chemotherapy

Abstract: For accurate assessment of the response to primary chemotherapy (PCT) for locally advanced breast cancer, we measured reduction in total tumor volume (TTV) by using three‐dimensional magnetic resonance imaging (3D MRI), and examined the relationship between this reduction and patient prognosis. Fifty‐one patients with locally advanced breast cancer were treated with four cycles of docetaxel (60 mg/m²) before surgery. Tumor size was measured with calipers, ultrasonography (US) and conventional two‐dimensional (2D) MRI before and after chemotherapy. TTV was measured with 3D MRI. These and other clinicopathological parameters were statistically analyzed to determine the prognosis for the patients. Median follow‐up time was 46 months (1–64 months). Of the 51 patients, 25 developed distant recurrences. Patients whose TTV decreased by 75% or more after PCT showed significantly better prognosis than others, while tumor size measured with calipers, US and 2D MRI showed no significant relationship with patient prognosis. Of the clinicopathological parameters, only reduction in TTV and histological grade showed a significant association with distant recurrence‐free survival (p = 0.03 and 0.02, log‐rank test), while stepwise multivariate Cox’s proportional hazards analysis identified TTV as the strongest independent prognostic factor. Reduction in TTV measured with 3D MRI can be a useful prognostic factor for patients with locally advanced breast cancer treated with PCT.     

Sentinel Lymph Node Biopsy Alone Has No Adverse Impact on the Survival of Patients with Breast Cancer

Abstract:   We do not yet know the results from multicenter randomized trials comparing survival after sentinel lymph node biopsy (SLNB) alone and axillary lymph node dissection (ALND). Therefore, in this study, the prognostic significance of the type of axillary surgery is analyzed in combination with other known prognostic factors in patients with breast cancer. In a series of 1325 consecutive patients with unilateral breast cancer who underwent SLNB between January 1999 and June 2004 at a single institution, 884 underwent SLNB alone following an intraoperative negative histologic investigation and 441 underwent ALND. Disease-free survival (DFS) and overall survival (OS) were analyzed to correlate with clinicopathologic features and treatment methods using both univariate and multivariate analyses Cox proportional hazard regression models. With a median follow-up period of 31 months, 29 (3.3%) and 37 (8.4%) patients relapsed after SLNB alone and ALND, respectively. Tumor size (Tis, T1–2 versus T3–4), histologic nodal involvement (negative versus positive), nuclear grade (NG) (1, 2 versus 3), lymphatic vessel invasion (LVI) (absent, weak versus intense), estrogen receptor (ER) status (positive versus negative), type of axillary surgery (SLNB alone versus ALND), type of breast surgery (partial versus total mastectomy), and radiation therapy (yes versus no) significantly correlated with DFS by univariate analysis, demonstrating better DFS in the former category than the latter for each variable. The multivariate analysis revealed that NG, LVI, ER status, and radiation therapy significantly correlated with DFS, and ER and histologic nodal involvement correlated with OS. As the type of axillary surgery had no impact on the prognosis of patients with breast cancer, a SLNB alone is safe as determined by a negative histologic investigation.      

Primary Breast Angiosarcoma: A Retrospective Study of 36 Cases from a Single Chinese Medical Institute with Clinicopathologic and Radiologic Correlations

The aim of this study was to present our experience with primary breast angiosarcoma (PBA) by describing a large series of cases with an emphasis on clinicopathologic and radiologic correlations. Thirty‐six cases of PBA diagnosed at our institution between 2006 and 2014 were retrospectively evaluated. All but one case occurred in women with a median age of 35.5 years. The majority of patients presented with a deeply located painless mass, whereas a minority manifested as diffuse enlargement or swelling of the breast. Magnetic resonance imaging showed poorly demarcated lesions with low signal intensity on T1‐weighted images, markedly high intensity on T2‐weighted images, and prolongation of enhancement upon dynamic study. Histologically, 19 cases (52.8%) were low grade, 12 cases (33.3%) were intermediate grade, and 5 cases (13.9%) were high grade. Follow‐up information was available for 27 patients and revealed local recurrence and/or metastasis in 16 patients (59.3%). Five patients (18.5%) died of the disease at a median interval of 20 months. Univariate analysis showed that tumor differentiation had effect on disease‐free survival (DFS) (p = 0.005) but failed to predict overall survival (OS) (p = 0.645). The treatment modality was related to OS (p = 0.042) but not DFS (p = 0.131). The Cox proportional hazards regression model suggested that tumor differentiation was an independent predictor of DFS (p = 0.015). We hypothesize that tumor differentiation may be used as a prognostic factor for this rare malignancy. Clinicopathologic and radiologic correlation may help pathologists to arrive at the correct diagnosis of PBA.     

A Population‐Based Cross‐Sectional Study Comparing Breast Cancer Stage at Diagnosis between Immigrant and Canadian‐Born Women in Ontario

There is limited information on stage at breast cancer diagnosis in Canadian immigrant women. We compared stage at diagnosis between immigrant women and Canadian‐born women, and determined whether ethnicity was an independent factor associated with stage. 41,213 women with invasive breast cancer from 2007 to 2012 were identified from the Ontario Cancer Registry. Women were classified as either immigrants or Canadian‐born by linkage with the Immigration, Refugees, and Citizenship Canada's Permanent Resident database. Women's ethnicity was classified as Chinese, South Asian, or remaining women in Ontario. Logistic regression was performed to calculate the odds ratio (OR) of being diagnosed at stage I breast cancer (versus stage II–IV). 4,353 (10.6%) women were immigrants and 36,860 (89.4%) were Canadian‐born women. The mean age at breast cancer diagnosis was 53.5 years for immigrants versus 62.3 years for Canadian‐born women (p < 0.0001). Immigrant women were less likely than Canadian‐born women to be diagnosed with stage I breast cancers (adjusted OR = 0.85; 95% CI: 0.79–0.91; p < 0.0001). The adjusted OR of being stage I was 1.28 (95% CI: 1.14–1.43; p < 0.0001) for women of Chinese ethnicity and was 0.82 (95% CI: 0.70–0.96; p = 0.01) for women of South Asian ethnicity, compared to the remaining women in Ontario. Canadian immigrant women were less likely than Canadian‐born women to be diagnosed with early‐stage breast cancers. Ethnicity was a greater contributor to the stage disparity than was immigrant status. South Asian women, regardless of immigration status, might benefit from increased breast cancer awareness programs.     

No Survival Benefit for Patients with Treatment in Certified Breast Centers—A Population‐based Evaluation of German Cancer Registry Data

Much time and money has been spent on the establishment and preservation of certified breast centers (CBCs), but up to now there is almost no evidence for whether certification results in an improved outcome for breast cancer patients. The aim of this evaluation was to assess, whether the certification of specialized units had any influence on their patients’ outcomes and if a survival difference between CBC patients and non‐CBC patients can be shown. This population‐based analysis included cancer registry data from 32,789 operated breast cancer patients with no prior cancer diagnosis and with active follow‐up. They were diagnosed between 2004 and 2010 in four different regions in Germany. Survival was investigated using the Kaplan–Meier method and multivariate Cox regression analysis. A survival difference was found neither between patients with treatment before and after certification of specialized units nor between CBC patients and non‐CBC patients aged up to 75 years. Only for patients older than 75 years, an improved survival could be seen for CBC patients (adjusted hazard ratio 0.77; 95% confidence interval 0.68–0.87). The improved survival of elderly CBC patients is most likely caused by selection effects concerning health status differences and not by processes attributable to certification. Thus, this study found that as of yet, certification has not influenced survival of breast cancer patients.     

Survival after Breast‐Conserving Surgery with Whole Breast or Partial Breast Irradiation in Women with Early Stage Breast Cancer: A SEER Data‐base Analysis

Randomized clinical trials have demonstrated equivalency in survival outcomes for early stage breast cancer patients treated with either mastectomy or breast‐conserving surgery (BCS) with radiation. Recent, state‐level data confirm comparable survival outcomes. Using Surveillance Epidemiology and End Research (SEER) data, we sought to evaluate survival outcomes among patients with early stage breast cancer treated with mastectomy, BCS with whole breast irradiation (BCS + WBI), or BCS with accelerated partial breast irradiation (BCS + APBI). Data on women 50 years or older diagnosed with a node negative invasive breast cancer (≤3 cm in size) between 1995 and 2009 were extracted from the SEER data base. Women treated with mastectomy alone or BCS with radiation were eligible for analysis. Kaplan–Meier estimates and Cox proportional hazard models were used to compare overall survival (OS) and cancer‐specific survival (CSS) among the treatment groups. 150,171 women fulfilled inclusion criteria. OS was significantly improved among women treated with BCS and WBI or BCS and APBI compared to mastectomy alone. Adjusted hazard ratios for death in BCS with WBI or APBI (versus mastectomy alone) were 0.73 (95% CI: 0.71, 0.76) and 0.68 (95% CI: 0.58, 0.79), respectively. Adjusted CSS was also significantly improved in patients treated with BCS and WBI (HR 0.80, 95% CI: 0.76, 0.85) as compared to mastectomy. BCS with radiation (WBI or APBI) was associated with significantly improved OS and CSS, versus mastectomy alone. These results support the use of BCS with WBI or APBI (in well selected patients) for the treatment of breast cancer.     

Long‐term Treatment with Intravenous Bisphosphonates in Metastatic Breast Cancer: A Retrospective Study

Bisphosphonates are important therapies used to reduce the risk of skeletal‐related events in patients with bone metastases from breast cancer (BC). This retrospective cohort study evaluated the incidence of osteonecrosis of the jaw (ONJ) and renal impairment in women (n = 221) with bone metastases from BC treated with intravenous bisphosphonates from January 1999 to June 2008. In the long‐term cohort, 159 patients received pamidronate (n = 9), zoledronic acid (n = 110), or both (n = 40) for ≥24 months. The comparator group consisted of patients treated with intravenous bisphosphonates for 12–23 months (n = 62). After 39 months' median follow‐up, six of 159 patients developed ONJ (3.8%; median 38.5 treatment cycles and 44 months' exposure) in the long‐term cohort. Of patients who developed ONJ, 50% resumed intravenous bisphosphonates after a 12‐month treatment holiday. Renal impairment developed in 19 patients in the long‐term cohort (11.9%; median 26 treatment cycles and 26 months' exposure). Of these 19 patients, 11 (57.9%) recovered baseline renal function and seven (36.7%) showed partial recovery. After modification of the intravenous bisphosphonate regimen, 17 of 19 patients (89.4%) resumed therapy. Of the 62 patients in the comparator cohort, one patient developed ONJ (1.6%) and six developed renal impairment (9.7%). Similar incidence rates of ONJ and renal impairment were observed for the long‐term and comparator cohorts. Times to ONJ or renal impairment also were similar across intravenous bisphosphonate type. Long‐term (≥24 months) intravenous bisphosphonate use in metastatic BC is well tolerated, with low incidences of ONJ and renal impairment.     

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.     

Clinical Characteristics of Breast Cancers in African‐American Women with Benign Breast Disease: A Comparison to the Surveillance,Epidemiology, and End Results Program

Benign breast disease (BBD) is a very common condition, diagnosed in approximately half of all American women throughout their lifecourse. White women with BBD are known to be at substantially increased risk of subsequent breast cancer; however, nothing is known about breast cancer characteristics that develop after a BBD diagnosis in African‐American women. Here, we compared 109 breast cancers that developed in a population of African‐American women with a history of BBD to 10,601 breast cancers that developed in a general population of African‐American women whose cancers were recorded by the Metropolitan Detroit Cancer Surveillance System (MDCSS population). Demographic and clinical characteristics of the BBD population were compared to the MDCSS population, using chi‐squared tests, Fisher's exact tests, t‐tests, and Wilcoxon tests where appropriate. Kaplan–Meier curves and Cox regression models were used to examine survival. Women in the BBD population were diagnosed with lower grade (p = 0.02), earlier stage cancers (p = 0.003) that were more likely to be hormone receptor‐positive (p = 0.03) compared to the general metropolitan Detroit African‐American population. In situ cancers were more common among women in the BBD cohort (36.7%) compared to the MDCSS population (22.1%, p < 0.001). Overall, women in the BBD population were less likely to die from breast cancer after 10 years of follow‐up (p = 0.05), but this association was not seen when analyses were limited to invasive breast cancers. These results suggest that breast cancers occurring after a BBD diagnosis may have more favorable clinical parameters, but the majority of cancers are still invasive, with survival rates similar to the general African‐American population.