Unilateral Primary Breast Cancer Research Articles

Long-term cardiovascular disease risk after anthracycline and trastuzumab treatments in US breast cancer survivors.

Although breast cancer survivors are at risk for cardiovascular disease (CVD) from treatment late effects, evidence to inform long-term and age-specific cardiovascular surveillance recommendations is lacking. We conducted a retrospective cohort study of 10 211 women diagnosed with first primary unilateral breast cancer in Kaiser Permanente Washington or Colorado (aged 20 years and older, survived ≥1 year). We estimated multivariable adjusted hazard ratios (HRs) for associations between initial chemotherapy regimen type (anthracycline and/or trastuzumab, other chemotherapies, no chemotherapy [referent]) and CVD risk, adjusted for patient characteristics, other treatments, and CVD risk factors. Cumulative incidence was calculated considering competing events. After 5.79 median years, 14.67% of women developed CVD (cardiomyopathy and/or heart failure [HF], ischemic heart disease, stroke). Women treated with anthracyclines and/or trastuzumab had a higher risk of CVD compared with no chemotherapy (adjusted HR = 1.53, 95% confidence interval [CI] = 1.31 to 1.79), persisting at least 5 years postdiagnosis (adjusted HR5-<10 years = 1.85, 95% CI = 1.44 to 2.39; adjusted HR≥10 years = 1.83, 95% CI = 1.34 to 2.49). Cardiomyopathy and/or HF risks were elevated among women treated with anthracyclines and/or trastuzumab compared with no chemotherapy, especially for those aged younger than 65 years (adjusted HR20-54years = 2.97, 95% CI = 1.72 to 5.12; adjusted HR55-64years = 2.21, 95% CI = 1.52 to 3.21), differing for older women (adjusted HR≥65 years = 1.32, 95% CI = 0.97 to 1.78), and at least 5 years postdiagnosis (adjusted HR5-<10years = 1.89, 95% CI = 1.35 to 2.64; adjusted HR≥10 years = 2.21, 95% CI = 1.52 to 3.20). Anthracyclines and/or trastuzumab receipt was associated with increased ischemic heart disease risks after 5 or more years (adjusted HR5-<10years = 1.51, 95% CI = 1.06 to 2.14; adjusted HR≥10 years = 1.86, 95% CI = 1.18 to 2.93) with no clear age effects, and stroke risk (adjusted HR = 1.33, 95% CI = 1.05 to 1.69), which did not vary by time or age. There was some evidence of long-term cardiomyopathy and/or HF and ischemic heart disease risks with other chemotherapies. Among women aged younger than 65 treated with anthracyclines and/or trastuzumab, up to 16% developed CVD by 10 years (20-54 years = 6.91%; 55-64 years = 16.00%), driven by cardiomyopathy and/or HF (20-54 years = 3.90%; 55-64 years = 9.78%). We found increased long-term risks of cardiomyopathy and/or HF and ischemic heart disease among breast cancer survivors treated with anthracyclines and/or trastuzumab and increased cardiomyopathy and/or HF risk among women aged younger than 65 years.

Risk of contralateral breast cancer among Asian/Pacific Islander women in the United States.

While breast cancer studies often aggregate Asian/Pacific Islander (API) women, as a single group or exclude them, this population is heterogeneous in terms of genetic background, environmental exposures, and health-related behaviors, potentially resulting in different cancer outcomes. Our purpose was to evaluate risks of contralateral breast cancer (CBC) among subgroups of API women with breast cancer. We conducted a retrospective cohort study of women ages 18 + years diagnosed with stage I-III breast cancer between 2000 and 2016 in the Surveillance, Epidemiology and End Results registries. API subgroups included Chinese, Japanese, Filipina, Native Hawaiian, Korean, Vietnamese, Indian/Pakistani, and other API women. Asynchronous CBC was defined as breast cancer diagnosed in the opposite breast 12 + months after first primary unilateral breast cancer. Multivariable-adjusted subdistribution hazard ratios (SHR) and 95% confidence intervals (CI) were estimated and stratified by API subgroups. From a cohort of 44,362 API women with breast cancer, 25% were Filipina, 18% were Chinese, 14% were Japanese, and 8% were Indian/Pakistani. API women as an aggregate group had increased risk of CBC (SHR 1.15, 95% CI 1.08-1.22) compared to NHW women, among whom Chinese (SHR 1.23, 95% CI 1.08-1.40), Filipina (SHR 1.37, 95% CI 1.23-1.52), and Native Hawaiian (SHR 1.69, 95% CI 1.37-2.08) women had greater risks. Aggregating or excluding API patients from breast cancer studies ignores their heterogeneous health outcomes. To advance cancer healthequity among API women, future research should examine inequities within the API population to design interventions that can adequately address their unique differences.

Validation of the PREDICT Prognostication Tool in US Patients With Breast Cancer.

PREDICT is an online prognostication tool derived from breast cancer registry information on approximately 6,000 women treated in the United Kingdom that estimates the postsurgical treatment benefit of surgery alone, chemotherapy, trastuzumab, endocrine therapy, and/or adjuvant bisphosphonates in early-stage breast cancer. Our aim was to validate the PREDICT algorithm in predicting 5- and 10-year overall survival (OS) probabilities using real-world outcomes among US patients with breast cancer. A retrospective study was performed including women diagnosed with unilateral breast cancer in 2004 through 2012. Women with primary unilateral invasive breast cancer were included. Patients with bilateral or metastatic breast cancer, no breast surgery, or missing critical clinical information were excluded. Prognostic scores from PREDICT were calculated and external validity was approached by assessing statistical discrimination through area under time-dependent receiver-operator curves (AUC) and comparing the predicted survival to the observed OS in relevant subgroups. We included 708,652 women, with a median age of 58 years. Most patients were White (85.4%), non-Hispanic (88.4%), and diagnosed with estrogen receptor-positive breast cancer (79.6%). Approximately 50% of patients received adjuvant chemotherapy, 67% received adjuvant endocrine therapy, 60% underwent a partial mastectomy, and 59% had 1 to 5 axillary sentinel nodes removed. Median follow-up time was 97.7 months. The population's 5- and 10-year OS were 89.7% and 78.7%, respectively. Estimated 5- and 10-year median survival with PREDICT were 88.3% and 73.8%, and an AUC of 0.77 and 0.76, respectively. PREDICT performed most poorly in patients with high Charlson-Deyo comorbidity scores (2-3), where PREDICT overestimated OS. Sensitivity analysis by year of diagnosis and HER2 status showed similar results. In this prognostic study utilizing the National Cancer Database, the PREDICT tool accurately predicted 5- and 10-year OS in a contemporary and diverse population of US patients with nonmetastatic breast cancer.

Abstract P3-05-30: Survival after Development of Contralateral Breast Cancer

Abstract Purpose There are many studies reporting survival after development of contralateral breast cancer(CBC) but with inconsistent results. Also, many studies were based on European or North American population and few on Asian population. However, Korean breast cancer patients have different characteristics such as age distribution. Therefore, purpose of this study is to investigate whether development of CBC has influence on survival in Korean breast cancer population. Methods In this retrospective study, we included patients who were diagnosed with a first primary unilateral non-metastatic breast cancer at Asan Medical Center, Korea, between 1999-2013 followed through 2018. In this population, patients who delveloped CBC during the follow-up period were divided into the CBC cohort, and who did not into the non-CBC cohort. Survival of CBC cohort and non-CBC cohort was compared in the whole study population and in subgroup analysis by interval of CBC development, and breast cancer subtype. Results Over median follow-up of 107 months, 418 patients developed CBC out of 16,251 patients. Development of CBC did not influence overall survival or breast cancer-specific survival. In subgroup analysis by interval of CBC development, patients who developed CBC within one year after diagnosis of the first breast cancer had higher risk for overall death in CBC cohort (hazard ratio 2.58; 95% CI 1.28-5.18), and patients who developed CBC after one year showed no significant difference in survival compared with non-CBC cohort. In subgroup analysis by the subtype, patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative subtype for the first breast cancer showed higher risk for overall death in CBC cohort (hazard ratio 1.88; 95% CI 1.14-3.10) whereas patients with triple negative subtype for the first breast cancer showed lower risk for overall survival in CBC cohort (hazard ratio 0.42; 95% CI 0.19-0.95). Conclusion Development of CBC in Korean breast cancer patients did not have significant impact on survival. However, development of CBC early after diagnosis of first breast or having certain subtype of breast cancer may have affect on survival. Such information can be important information when counseling patients who are considering contralateral prophylactic mastectomy. Citation Format: Hakyoung Kim, Hee Jeong Kim, Yoon Tae In, Seonok Kim, Sae Byul Lee, Jisun Kim, Il-Yong Chung, Beom Seok Ko, Jong Won Lee, Byung Ho Son, Sei Hyun Ahn. Survival after Development of Contralateral Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-30.

Altona Prognostic Index: A New Prognostic Index for ER-Positive and Her2-Negative Breast Cancer of No Special Type.

Simple SummaryBreast cancer is the most common tumor-related cause of death in women in Europe and worldwide. The aim of our retrospective study, including 6654 women, was on the one hand to verify the validity of the worldwide known Nottingham prognostic index (NPI), and on the other hand to create a new model with even more prognostic validity. Our newly developed Altona prognostic index (API) shows significantly superior outcome in calculating progression free survival. In contrast to the NPI, the API considers characteristics such as subtypes of breast cancer, as this disease is heterogenous involving different entities, and patient’s age. Evaluating progression free survival in different subgroups, our study shows that both these prognostic indices should only be applied on a patient collective that is ≤70 years old with first primary, unifocal, unilateral breast cancer that is of no special type (NST), estrogen receptor-positive and Her2-negative to get valid prediction data. Breast cancer is a heterogeneous disease representing a number of different histopathologic and molecular types which should be taken into consideration if prognostic or predictive models are to be developed. The aim of the present study was to demonstrate the validity of the long-known Nottingham prognostic index (NPI) in a large retrospective study (n = 6654 women with a first primary unilateral and unifocal invasive breast cancer diagnosed and treated between April 1996 and October 2018; median follow-up time of breast cancer cases was 15.5 years [14.9–16.8]) from a single pathological institution. Furthermore, it was intended to develop an even superior risk stratification model considering an additional variable, namely the patient’s age at the time of diagnosis. Heterogeneity of these cases was addressed by focusing on estrogen receptor-positive as well as Her2-negative cases and taking the WHO-defined different tumor types into account. Calculating progression free survival Cox-regression and CART-analysis revealed significantly superior iAUC as well as concordance values in comparison to the NPI based stratification, leading to an alternative, namely the Altona prognostic index (API). The importance of the histopathological tumor type was corroborated by the fact that when calculated separately and in contrast to the most frequent so-called “No Special Type” (NST) carcinomas, neither NPI nor API could show valid prognostic stratification.

A Comparison of the Diagnostic Value of Positron Emission Tomography/Computed Tomography and Ultrasound for the Detection of Metastatic Axillary Nodal Disease in Treatment-Naive Breast Cancer.

The objective of this study was to describe the diagnostic value of positron emission tomography/computed tomography (PET/CT) and ultrasound (US) for identifying metastatic axillary disease in primary breast cancer. This is a retrospective review of 240 patients with treatment-naive unilateral primary breast cancer of at least stage T2. Eighty-five patients met our inclusion criteria. Initial whole-body PET/CT and axillary US examinations were reviewed and compared with the criterion standard of fine-needle aspiration cytology. Sensitivity, accuracy, and positive predictive value (PPV) for each modality were computed. Because of all positive US cases, specificity and negative predictive value of US were not determined. Sensitivity and accuracy between modalities were compared using McNemar test. The majority of the patients were White women with clinical inflammatory breast cancer and with histologically invasive ductal carcinoma. The most common tumor and nodal stage was T4N3. The tumors were predominantly estrogen receptor positive, progesterone receptor negative, and human epidermal growth factor receptor 2 negative. The sensitivities of PET/CT and US were 96.2% and 100%, respectively. The accuracies for PET/CT and US were 91.8% and 94.1%, respectively. The PPV for PET/CT was 95.1%, and for US, the PPV was 94.1%. No significant difference in sensitivity or accuracy was shown between PET/CT and US for the diagnosis of metastatic axillary nodal disease. Three of 85 cases showed discordance between negative PET/CT and positive US and fine-needle aspiration cytology.

Variation in Breast Cancer Subtype Incidence and Distribution by Race/Ethnicity in the United States From 2010 to 2015

Breast cancer is the most commonly diagnosed cancer and the leading cause of death in women worldwide. Yet the racial/ethnic disparity in incidences and distributions of breast cancer remains largely unknown. To examine the racial/ethnic patterns associated with the incidence of the subtypes of breast cancer and distribution of patients across clinicopathological variables. This population-based cohort study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database, which collected data from 18 SEER cancer registries that identified patients with breast cancer in the US diagnosed between January 1, 2010, and December 31, 2015. The inclusion criteria were (1) female patients with primary unilateral breast cancer who underwent surgical treatment; (2) record of estrogen receptor, progesterone receptor, and ERBB2 status; (3) record of medical history and histological subtype of the specified tumor location; and (4) data on patient race/ethnicity, lateral tumor position, tumor size, tumor TNM stage, and number of tumors. Incidence and distribution rates were identified and compared for different molecular subtypes, histological grades, pathological patterns, T stages, TNM stages, and tumor sites of breast cancers for each racial/ethnic group. Patient race/ethnicity was classified as follows: non-Hispanic White, Hispanic White, Black, Asian/Pacific Islander, American Indian/Alaskan Native, and unknown. Data were analyzed from January 1, 2010, to December 31, 2015. Incidence rates of 4 molecular subtypes: hormone receptor (HR)-positive and ERBB2-negative, HR-positive and ERBB2-positive, HR-negative and ERBB2-positive, and triple-negative breast cancer (TNBC). Data on distribution by histological grades (grades 1-4 and unknown), pathological patterns, T stages, TNM stages, and tumor sites was also extracted. Annual age-standardized incidence rates and incidence rate ratios (IRRs) were calculated with 95% CIs. Race/ethnicity case-to-case odds ratios were estimated using polytomous regression. A total of 239 211 women with breast cancer were analyzed (median [interquartile range]) age, 60 [50-69] years). The annual incidence rate of all breast cancers was 31.3 (95% CI, 31.2- 31.5) per 100 000 people in non-Hispanic White women (the reference group), which was higher compared with the incidence among Black women (IRR, 1.04; 95% CI, 1.02-1.05; P < .001). The incidence rates were also lower in Asian/Pacific Islander (IRR, 0.90; 95% CI, 0.89-0.92; P < .001), American Indian/Alaskan native (IRR, 0.82; 95% CI, 0.81-0.83; P < .001), and Hispanic White women (IRR, 0.79; 95% CI, 0.75-0.83; P < .001). In Black patients, the incidences of the HR-positive and ERBB2-positive (IRR, 1.12; 95% CI, 1.08-1.16; P < .001), HR-negative and ERBB2-positive (IRR, 1.46; 95% CI, 1.38-1.54; P < .001), and TNBC (IRR, 2.07; 95% CI, 2.01-2.14; P < .001) subtypes were higher than those in non-Hispanic White patients, but the incidence of the HR-positive and ERBB2-negative subtype in Black women was lower (IRR, 0.86; 95% CI, 0.84-0.87; P < .001). The incidences of histological grade 1 (IRR, 0.75; 95% CI, 0.73-0.78; P < .001) and grade 2 (IRR, 0.91; 95% CI, 0.89-0.93; P < .001) were lower in Asian/Pacific Islander vs non-Hispanic White patients. Non-Hispanic White patients had a higher proportion of lobular carcinoma (9.7% [n = 15 718]) and tubular adenocarcinoma (0.6% [n = 997]) than Black (7.2% [n = 1933]; 0.3% [n = 81]), Asian/Pacific Islander (5.7% [n = 1202]; 0.3% [n = 55]), Hispanic White (7.2% [n = 1985]; 0.3% [n = 88]), and American Indian/Alaskan Native patients (7.2% [n = 101]; 0.4% [n = 5]). This cohort study found notable disparities in incidences and proportions of different molecular subtypes, histological grades, pathological patterns, T stages, TNM stages, and tumor sites associated with race/ethnicity. The findings suggest that combining epidemiologic with genomic and molecular profiling data warrants further research.

A Retrospective Analysis of the Relationship Between the Result of BRCA1/2 Genetic Testing and Surgical Method Selection in Japan

BackgroundWe studied the extent of BRCA1/2 genetic testing to help select the surgical approach for patients with breast cancer in Japan remains unclear. Patients and MethodsThe study subjects were female patients with primary unilateral invasive breast cancer considered as candidates for breast-conserving surgery who underwent preoperative BRCA1/2 genetic testing. A retrospective analysis was performed on the results of BRCA1/2 genetic testing and surgical method selection using national registration data from the Japanese Hereditary Breast and Ovarian Cancer Syndrome Consortium. ResultsOur study included 318 female patients. Among these patients, 23.7% of patients with BRCA1/2 mutations and 61.8% of patients without these variants underwent breast-conserving surgery (P < .01). Among the patients with BRCA1/2 mutations, those who chose breast-conserving surgery tended not to undergo risk-reducing salpingo-oophorectomy (P < .05). Among the patients with BRCA1/2 mutations who underwent mastectomy for the affected side, 31.8% received contralateral risk-reducing mastectomy. Patients diagnosed with breast cancer under the age of 50 years were more likely to have contralateral risk-reducing mastectomy than patients over the age 50 years (P < .05). ConclusionsPatients with BRCA1/2 mutations tend to choose mastectomy. However, it is speculated that the final surgical method selection is made in consideration of not only the test results but also with careful consideration of the patient, taking into account other factors including individual values for risk-reducing surgeries and the age of breast cancer onset.

Abstract 5749: The association between physical health-related quality of life, physical functioning and risk of contralateral breast cancer

Abstract Background: Physical limitations and disability among older cancer patients can lead to suboptimal treatment and surveillance for secondary cancers. Our objective was to evaluate the effects of poor physical health-related quality of life (PQOL) and physical functioning (PF) on contralateral breast cancer (CBC) risk among older women diagnosed with unilateral breast cancer (UBC). Methods: We performed a nested case-control study within a cohort from the Surveillance, Epidemiology and End Results Medicare Health Outcomes Survey (MHOS) database. Women were required to have first primary UBC without prophylactic contralateral mastectomy. Among 2,938 women ages 65 years and older with stages I-III UBC between 1997 and 2011, we identified 100 subsequent CBC cases and 915 controls using incidence density sampling without replacement matched on age, race, and quarter-year of diagnosis. PQOL and PF were determined from survey responses to the Medical Outcomes Trust Short Form 36 component scores. Conditional logistic regression models were used to estimate relative risks (RR) and 95% confidence intervals (CI) for metachronous CBC. Results: Cases and controls were similar with respect to comorbidities, stage, surgery and radiation treatments but differed by hormone receptor status (ER/PR-negative, cases 23% and controls 11%). Cases had lower mean PQOL (-1.8; 95% CI -4.3, 0.7) and PF (-2.2, 95% CI -4.9, 0.5) component scores, but these differences were not statistically significant. In multivariable models, estimates suggest increased CBC risk for women in the lowest quartile of PQOL compared to those in the upper quartile (RR=1.8; 95% CI 0.8, 4.3). Compared to women in the upper quartile of physical functioning scores, women in the lower three quartiles had a 2.6-fold (95% CI 1.2, 5.9) increased risk of CBC. Conclusions: Our findings indicate that low physical health-related quality of life is common among older women diagnosed with breast cancer, and poor physical functioning is related to risk of CBC. Efforts to understand and minimize declines in physical functioning post-breast cancer diagnosis may help optimize treatment strategies to reduce the risk of this adverse outcome. Citation Format: Nita Mukand, Nadia Nabulsi, Ali Alobaidi, Alemseged Asfaw, Brian C. Chiu, Naomi Y. Ko, Gregory S. Calip. The association between physical health-related quality of life, physical functioning and risk of contralateral breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5749.

Investigation of the pathomechanism of smoke-induced pancreatic damage

The need for completion axillary lymph node dissection (ALND) in breast cancer patients with micrometastases in the sentinel nodes (SNs) is controversial. The aim of this retrospective observational study is to determine if the method of detection of early breast cancer is predictive for additional positive nodes in patients with micrometastases in the SNs.Between 2001 and 2011 a total of 1993 women with primary unilateral breast cancer had surgery at Skåne University Hospital, Lund. Of 1993 patients, 1458 had an SN biopsy and nearly all patients with micro- and macrometastases had ALND.Micrometastases defined as >0.2 mm/>200 cells and ≤2.0 mm were found in 62 of 757 screen-detected patients and in 81 of 701 patients with symptomatic breast cancer. Only 3 of the screen-detected patients with micrometastases, all with tumour size >15 mm (range 18–39 mm), had metastases in the completion ALND whereas this was found in 18 of the symptomatic patients with micrometastases (p = 0.01), (tumour size, range 10–30 mm). Logistic regression analysis adjusted for method of detection, tumour size and histological grade showed 5 times higher odds for further metastases in ALND in patients with symptomatic presentation vs. screen-detected breast cancer.Despite the small number of patients with micrometastases in this large cohort of breast cancer patients, these results support the contention that completion ALND can safely be omitted in screen-detected breast cancer patients with micrometastases in the SNs.

3275 Nonclinical factors associated with contralateral prophylactic mastectomy among breast cancer patients in the Surveillance, Epidemiology, and End Results (SEER) database

OBJECTIVES/SPECIFIC AIMS: The study aims to measure the associations between nonclinical factors and the likelihood of electing contralateral prophylactic mastectomy [(CPM) i.e. bilateral mastectomy for unilateral cancer] among women with breast cancer, with a focus on the roles of race, relationship status, and geographic location. The outcome of interest is a dichotomized surgery type variable (i.e. CPM versus other surgery). METHODS/STUDY POPULATION:. The Surveillance, Epidemiology, and End Results registry was queried to identify female breast cancer patients diagnosed at stage IA through IIIC from 2010 through 2015 and received surgery as part of their primary treatment (n=174,776). A multilevel logistic regression was used to model likelihood of CPM versus less aggressive surgical treatment (i.e. breast conserving surgery or unilateral mastectomy). Fixed-effects included age at diagnosis, race, relationship status, insurance type, county-level median income, county-level population density, stage at diagnosis (low-stage, IA-IIB; advanced-stage, IIIA-IIIC), an interaction term between race and stage at diagnosis, and breast tumor subtype. County of residence was used as a random-effect. RESULTS/ANTICIPATED RESULTS: Among women with low-stage cancer, compared to the reference class of white women, black women had 0.57 times lower odds of CPM (p&lt;0.0001), Hispanic women had 0.69 times lower odds of CPM (p&lt;0.0001), and Asian women had 0.60 times lower odds of CPM (p&lt;0.0001). Among women with advanced-stage cancer, compared to white women, black women had 0.42 times lower odds of CPM (p&lt;0.0001), Hispanic women had 0.51 times lower odds of CPM (p&lt;0.0001), and Asian women had 0.45 times lower odds of CPM (p&lt;0.0001). Compared to the reference class of single, never-married women, divorced/separated women had 1.25 times greater odds of CPM (p&lt;0.0001), widowed women had 1.11 times greater odds of CPM (p=0.009), and married/partnered women had 1.18 times greater odds of CPM (p&lt;0.0001). County-level variation from the random-effect (MOR, 1.49; p&lt;0.001) had a greater influence on CPM election than fixed-effects for insurance class, breast tumor subtype, county median income, county population density, and year of surgery. DISCUSSION/SIGNIFICANCE OF IMPACT: The nonclinical factors associated with variation in breast cancer surgical decision-making suggest patients and providers both may benefit from further education about surgical treatment options. Providers may also benefit from educational materials that highlight treatment selection disparities within specific contexts, such as surgery for primary unilateral breast cancer. To more narrowly tailor future policy interventions, an additional mixed-methods exploration is recommended to clarify how relationship status and location serve as mechanisms for breast cancer decision-making.

Regional Recurrence Risk Following a Negative Sentinel Node Procedure Does Not Approximate the False-Negative Rate of the Sentinel Node Procedure in Breast Cancer Patients Not Receiving Radiotherapy or Systemic Treatment.

Although the false-negative rate of the sentinel lymph node biopsy (SLNB) in breast cancer patients is 5-7%, reported regional recurrence (RR) rates after negative SLNB are much lower. Adjuvant treatment modalities probably contribute to this discrepancy. This study assessed the 5-year RR risk after a negative SLNB in the subset of patients who underwent breast amputation without radiotherapy or any adjuvant treatment. All patients operated for primary unilateral invasive breast cancer between 2005 and 2008 were identified in the Netherlands Cancer Registry. Patients with a negative SLNB who underwent breast amputation and who were not treated with axillary lymph node dissection, radiotherapy, or any adjuvant systemic treatment were selected. The cumulative 5-year RR rate was estimated by Kaplan-Meier analysis. A total of 13,452 patients were surgically treated for primary breast cancer and had a negative SLNB, and 2012 patients fulfilled the selection criteria. Thirty-eight RRs occurred during follow-up. Multifocal disease was associated with a higher risk of developing RR (P = 0.04). The median time to RR was 27months and was significantly shorter in patients with estrogen receptor-negative (ER-) breast cancer (9.5months; P = 0.003). The 5-year RR rate was 2.4% in the study population compared with 1.1% in the remainder of 11,440 SLNB-negative patients (P = 0.0002). Excluding the effect of radiotherapy and systemic treatment resulted in a twofold 5-year RR risk in breast cancer patients with a tumor-free SLNB. This 5-year RR rate was still much lower than the reported false-negative rate of the SLNB procedure.

Efficacy and safety of TE/TEC/intensive paclitaxel neoadjuvant chemotherapy for the treatment of breast cancer.

Efficacy and safety of paclitaxel/docetaxel + epirubicin (TE), paclitaxel/docetaxel + epirubicin + cytoxan (TEC) and intensive paclitaxel (IP) neoadjuvant chemotherapy (NCT) were compared for the treatment of breast cancer. The clinical data of 326 patients with stage II–III unilateral primary breast cancer treated in Shengjing Hospital of China Medical University from January 2012 to April 2016 were retrospectively analyzed. All patients received NCT for 4 cycles, including 115 cases of TE group, 109 cases of TEC group, and 102 cases of paclitaxel weekly group. The clinical efficacy was evaluated and complete response (CR) + partial response (PR) indicated clinically effective. The pathological effect was evaluated and the grade III+IV+V indicated pathologically effective. The rates of clinical efficacy and pathological CR (pCR) were compared, and the incidence of adverse reactions was also observed. The effects of different molecular typing on clinical efficacy and pCR were compared. Our results showed that the clinical effective rates in TE, TEC and IP groups were 80.9, 89.0 and 77.5%, respectively, and there were no statistically significant differences (P=0.074). The pCR rates in the three groups were 9.57, 8.26 and 5.88%, respectively, and the differences were not statistically significant (P=0.602). The incidence rate of neutropenia was statistically different among the three groups of patients (P<0.001), which was the highest in TEC group and the lowest in IP group. There were no statistically significant differences in the incidence rates of adverse reactions (P>0.05). Estrogen receptor (ER)-negative, progesterone receptor (PR)-negative and human epidermal growth factor receptor-2 (HER-2)-positive states were significantly correlated with the high clinical effective rate and high pCR rate (P<0.05). In conclusion, IP has the lowest incidence rate of neutropenia. Additionally, ER-negative, PR-negative and HER-2-positive states are significantly correlated with the high clinical effective rate and high pCR rate.

Cost effectiveness analysis of Oncotype DX testing in patients with synchronous unilateral primary breast cancer.

e12555Background: Oncotype DX is a commercial diagnostic test used to predict the likely benefit from chemotherapy in ER+ HER2- node- breast cancer. Patients with multiple, synchronous ipsilateral ...

Abstract P2-10-10: Oncotype Dx testing in patients with synchronous unilateral primary breast cancer

Abstract Introduction: Oncotype DX, is a commercial diagnostic test that is used to predict the likely benefit from chemotherapy in ER+, HER2-negative, node-negative breast cancer. Patients with multiple, synchronous ipsilateral primary breast cancers often have &amp;gt;1 tumor tested if results from the first tumor show low or intermediate recurrence scores. Whether this approach is cost effective is unknown. Methods: We reviewed Oncotype Dx results for 907 ER+/HER2- breast cancer patients seen at Rush University Medical Center from 2/2006 to 10/2016. Thirty-nine patients (35 with the same histology) had multiple, synchronous unilateral tumor samples tested. Results were reported both on the numeric risk score associated with the test and the categorized result (low/intermediate/high) recurrence risk. For patients undergoing more than 2 tests, the first two were arbitrarily chosen for the paired analysis. Descriptive statistics were used to examine the risk score distributions and assess potential correlation between paired samples. Statistical inference methods included estimating the correlation coefficient, regression models predicting one score with another, and evaluating the paired score differences with respect to mean deviation from zero. For categorized risk score, analysis evaluating category concordance between tumors was used to assess the degree of agreement. Analyses were conducted on all patients, and a subset consisting of patients whose two tumors had the same histology, where scores may be expected to exhibit greater concordance. Results:Categorical risk score (RS): The concordance rate for risk category was 77% (30/39 patients) and Kendall's tau measure of association = 0.57, and was further increased to 80% (28/35 patients) and tau 0.63 for tumors with the same histology. Only one patient had tumor samples with low and high RS. A second patient had tumor samples with intermediate and high RS. Continuous RS: The correlation was 0.81 (p &amp;lt; 0.0001). For tumors with the same histology, correlation increased to 0.83, with regression r2 (predicting second tumor RS value with first) = 0.69, indicating that the majority of variation in second score can be explained by variation in first score. Conclusion: Oncotype Dx testing in patients with synchronous, unilateral primary breast cancers generally results in concordant results, even more so when the tumor samples are of the same histology. In our study, only 1 of the 39 patients had discordant low/high tumor pairs. Continuous scale tumor RS scores were highly correlated (&amp;gt; 0.8). Therefore the benefit of testing additional samples appears marginal and, with the $4,620 cost per test, may not be cost-effective. Citation Format: Clark M, Coggan J, Dignam J, Rao R, Usha L, Kabaker K, Cobleigh M. Oncotype Dx testing in patients with synchronous unilateral primary breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-10-10.

Imaging Surveillance After Primary Breast Cancer Treatment.

Current clinical guidelines are consistent in supporting annual mammography for women after treatment of primary breast cancer. Surveillance imaging beyond standard digital mammography, including digital breast tomosynthesis (DBT), breast ultrasound, and MRI, may improve outcomes. This article reviews the evidence on the performance and effectiveness of breast imaging modalities available for surveillance after treatment of sporadic unilateral primary breast cancer and identifies additional factors to be considered when selecting an imaging surveillance regimen. Evidence review supports the use of mammography for surveillance after primary breast cancer treatment. Variability exists in guideline recommendations for surveillance initiation, interval, and cessation. DBT offers the most promise as a potential modality to replace standard digital mammography as a front-line surveillance test; a single published study to date has shown a significant decrease in recall rates compared with standard digital mammography alone. Most guidelines do not support the use of whole-breast ultrasound in breast cancer surveillance, and further studies are needed to define the characteristics of women who may benefit from MRI surveillance. The emerging evidence about surveillance imaging outcomes suggests that additional factors, including patient and imaging characteristics, tumor biology and gene expression profile, and choice of treatment, warrant consideration in selecting personalized posttreatment imaging surveillance regimens.

Aesthetic and functional outcome after breast conserving surgery – Comparison between conventional and oncoplastic resection

BackgroundRecent studies implicate that oncoplastic breast cancer surgery provides better aesthetic outcome than conventional resection. Several factors have been associated with poor aesthetic outcome. This study aims to compare patient-reported aesthetic and functional outcome after conventional and oncoplastic resection and to evaluate prognostic factors for poor aesthetic outcome in a population-based setting. Methods637 patients having breast conserving treatment (BCT) due to unilateral primary breast cancer at a single hospital district during 2010 were included. Aesthetic and functional outcome were evaluated using two questionnaires three years after surgery. ResultsQuestionnaires were returned by 379 (59%) patients; 293 (77%) of these had conventional and 86 (23%) oncoplastic resection. Patients in oncoplastic resection group had larger tumour diameter (p < 0.001), larger resection specimens (p < 0.001), and more often multifocal tumours (p = 0.032), node positive cancer (p = 0.029) and lower quadrant tumour localization (p = 0.007). Aesthetic outcome according to BCTOS questionnaire was good in 284 (75%) patients; 52 (61%) patients in the oncoplastic group and 230 patients (81%) in the conventional resection group, p < 0.001. Larger tumour diameter (p = 0.033), multifocality (p = 0.022), weight of resection specimen (<0.001) and oncoplastic surgery (p < 0.001) were predicting poor aesthetic outcome, when all patients were included. Tumour multifocality (p = 0.013) remained predictor of poor aesthetic outcome in conventional resection group but not in oncoplastic resection group. ConclusionsPatient satisfaction to aesthetic outcome after BCT is high. Conventional resection provides good aesthetic outcome in appropriately selected patients. Oncoplastic resection enables BCT in patients with larger and multifocal tumours with favourable aesthetic outcome.

Association of Adjuvant Tamoxifen and Aromatase Inhibitor Therapy With Contralateral Breast Cancer Risk Among US Women With Breast Cancer in a General Community Setting

Within 10 years after breast cancer diagnosis, roughly 5% of patients develop contralateral breast cancer (CBC). Randomized trials have found that therapy including tamoxifen citrate and aromatase inhibitors (AIs) reduces CBC risk. But little is known about the magnitude and duration of protective associations within the context of real-world clinical management settings, where varying durations of and gaps in treatment are common. To determine the association between adjuvant tamoxifen and AI therapy and CBC risk within a general community setting. A retrospective cohort study of CBC risk among 7541 patients diagnosed with a first primary unilateral invasive breast cancer at Kaiser Permanente Institute for Health Research (Colorado) or Kaiser Permanente Northwest Center for Health Research (Oregon) between January 1, 1990, and December 31, 2008. Data were analyzed from 1 year after diagnosis of the first breast cancer through the earliest of the following events: CBC diagnosis, other second cancer diagnosis, death, last tumor registry follow-up, exit from the Kaiser Permanente health care plan, or end of study follow-up (December 31, 2010, for Oregon and December 31, 2011, for Colorado). Adjuvant tamoxifen use and AI therapy were treated as time-dependent exposures, assessed using electronic prescription records. Incident CBC based on long-term systematic follow-up. Among 7541 women with invasive breast cancer, median age at initial breast cancer diagnosis was 60.6 years (age range, 24.9-84.9 years). Women were predominantly (92.9% [7009 of 7541]) of white race. During a median of 6.3 years (range, 1-20.9 years) of follow-up, 248 women developed CBC (45 in situ and 203 invasive). Contralateral breast cancer risk decreased significantly with increasing tamoxifen therapy duration. In current users, the relative risk (RR) per year of tamoxifen use was 0.76 (95% CI, 0.64-0.89), with an estimated 66% (RR, 0.34; 95% CI, 0.29-0.40) RR reduction for 4 years of use compared with nonusers. Risk reductions were slightly smaller for past users but were still significant at least 5 years after stopping tamoxifen therapy (RR per year of use, 0.85; 95% CI, 0.71-0.995). In addition, AI use without tamoxifen therapy was associated with reduced CBC risk (RR for AI users compared with nonusers, 0.48; 95% CI, 0.22-0.97). Risk reductions were most apparent among women whose primary and CBCs were estrogen receptor positive. Tamoxifen therapy was associated with reduced CBC risk during treatment and after its cessation, with risk progressively decreasing as tamoxifen therapy duration increased. Among those surviving at least 5 years, tamoxifen use for at least 4 years was estimated to prevent 3 CBCs per 100 women by 10 years after an estrogen receptor-positive first breast cancer, an absolute risk reduction that is consistent with findings from clinical trials. If adjuvant endocrine therapy is indicated for breast cancer treatment, these findings in concert with trial data suggest that women should be encouraged to complete the full course.

Contemporary Locoregional Recurrence Rates in Young Patients With Early-Stage Breast Cancer.

The aim of this study was to evaluate contemporary rates of local recurrence (LR) and regional recurrence (RR) in young patients with breast cancer in relation to tumor biology as expressed by biomarker subtypes. Women < 35 years of age who underwent surgery for primary unilateral invasive breast cancer between 2003 and 2008 were selected from the Netherlands Cancer Registry. Patients were categorized according to biomarker subtypes on the basis of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. The 5-year risks of developing LR and regional lymph node recurrence were estimated by using Kaplan-Meier statistics. A total of 1,000 patients were identified, of whom 59% had a known subtype: 39% HR-positive/HER2-negative; 17% HR-positive/HER2-positive; 10% HR-negative/HER2-positive; and 34% HR-negative/HER2-negative (triple negative). Overall 5-year LR and RR rates were 3.5% and 3.7%, respectively. A decreasing trend for both rates was observed over time and was accompanied by a significant decrease in the risk of distant metastases (DM). LR occurred in 4.2%, RR in 6.1%, and DM in 17.8% of patients in 2003, and in 3.2%, 4.4%, and 10.0%, respectively, in 2008. LR and RR rates varied with biomarker subtype. These differences were borderline significant when analyzed for the entire study period (P = .056 and P = .014, respectively) and leveled off after the introduction of trastuzumab after 2005 (P = .24 and P = .42, respectively). Patients with lymph node metastases at the time of diagnosis had an increased risk of RR. The type of surgery performed-breast-conserving or mastectomy-did not influence rates of LR and RR. Overall, the rates of LR and RR in young patients with early-stage breast cancer were relatively low and varied by biomarker subtype.

Contemporary risks of local and regional recurrence and contralateral breast cancer in patients treated for primary breast cancer

IntroductionBreast cancer treatment has evolved extensively over the past two decades with a shift towards less invasive local treatment and increased systemic treatment. The present study aimed to investigate the rates of local (LR) and regional (RR) recurrence and contralateral breast cancer (CBC), evaluating the influence of contributing factors. Materials and methodsWe selected all female patients operated for unilateral primary breast cancer (anyTN, M0) between 2003 and 2008 from the Netherlands Cancer Registry. The 5-year risks of developing LR, RR and CBC were estimated using Kaplan-Meier statistics. The influence of various patient, tumour and treatment characteristics was subsequently assessed in multivariable analyses. ResultsA total of 52,626 patients were identified. The rates of LR, RR and CBC were 2.7%, 1.5% and 2.9%, respectively. The rates of LR and RR decreased significantly over time in the period 2003–2008, from 3.2% to 2.4% for LR and 1.8 to 1.3% for RR, both becoming lower than the risk of CBC of 2.8%. Multivariable analysis showed that age, tumour size, lymph node involvement, tumour histologic type, grade and hormone receptor status were significant prognosticators for LR and RR, but not for CBC. A trend towards a beneficial effect of breast conserving surgery on LR and RR was seen, while systemic therapy proved to have a protective effect on all three end-points. ConclusionsIn breast cancer patients treated between 2003 and 2008 locoregional recurrence rates decreased and have ended up lower than the risk of developing CBC.