National Surgical Adjuvant Breast And Bowel Project Research Articles

Abstract PO4-01-03: Dual anti-HER2 Therapy with Pertuzumab and Trastuzumab versus Trastuzumab Alone in Addition to Anthracycline and Taxane-Based Neoadjuvant Therapy in Patients with HER2-Positive Early-Stage Breast Cancer; Real-World Data

Abstract Background: When use in the neoadjuvant setting, anti-HER2 targeted therapy had improved pathologic complete response rate (pCR) in patients with HER2-positive early-stage breast cancer (EBC). Here we present real-world data on the use trastuzumab with or without pertuzumab on the backbone of anthracycline and taxanes-based NSAPB-B27 chemotherapy regimen. Methods: We retrospectively reviewed records of patients with HER2-positive EBC who received neoadjuvant therapy using the National Surgical Adjuvant Breast and Bowel Project (NSABP)-B27 protocol (4 cycles of adriamycin and cyclophosphamide, followed by 4 more cycles of docetaxel; all given every 3 weeks) with anti-HER2 therapy from Jan 2014 to September 2021, treated at a tertiary care cancer center. The clinicopathological features, treatment received, and outcome were collected from patients’ electronic medical records. We estimated 3-year disease-free survival (DFS), a validated endpoint in HER2-positive EBC, using Kaplan-Meier with recurrence and/or death as events. Outcomes were reported in subgroups based on known prognostic factors. Results: The study comprised 528 patients with a median follow-up of 36 months. Median age was 48 (21-80) years. Hormone receptors (HR) were positive in 379 (71.8%), lymph node-involvement prior to neoadjuvant therapy was reported in 402 (76.1%) patients and 319 (60,4%) had grade-3 disease. Majority (n= 482, 91.3%) were labeled HER2-positive based on immunohistochemistry staining (IHC+3) and the rest were based on IHC+2 with positive FISH/ISH. Dual anti-HER2 therapy (trastuzumab and pertuzumab) was used in 316 (59.8%) patients, single agent trastuzumab in 173 (32.8 %) patients, while 39 (7.4%) others did not receive any anti-HER2 therapy. Except for 9 (1.7%) patients who progressed while on treatment, all patients underwent surgery. Among the whole group, 225 (43.4%) achieved pCR; significantly higher (n=80, 53.7%) in HR-negative compared to 38.3% among those with HR-positive disease, p=0.002. Additionally, pCR was higher in patients who received dual anti-HER2 (46.2%) compared to 39.3% for those treated with trastuzumab and 28.2% for those who did not receive anti-HER2 therapy. Following surgery, 463 (89.4%) of the patients received adjuvant trastuzumab, however, none of them received pertuzumab or TDM1 in adjuvant sitting. Estimated 3-year DFS was 86.1% with dual anti-HER2 and 83.0% with trastuzumab alone, p=0.19. However, DFS was better among those with node-negative disease; 96.5% compared to 80.9% in node-positive disease, p= < 0.001. Patients who achieved pCR had significantly better 3-year DFS; 89.3% compared to 80.2% in patients with residual disease, p= 0.006. Conclusions: Even with the wide use of pertuzumab in the neoadjuvant setting, the DFS was not improved compared to trastuzumab alone, and this highlights the importance of switching trastuzumab to TDM1, or to continue with pertuzumab in the adjuvant setting in patient with residual disease. Citation Format: Baha' Sharaf, Faris Tamimi, Osama Salama, Anas Zayed, Osama El Khatib, Suhaib Khater, Malek Horani, Suhaib Al-Sawajneh, Yosra AL-Masri, Hikmat Abdel-Razeq. Dual anti-HER2 Therapy with Pertuzumab and Trastuzumab versus Trastuzumab Alone in Addition to Anthracycline and Taxane-Based Neoadjuvant Therapy in Patients with HER2-Positive Early-Stage Breast Cancer; Real-World Data [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-01-03.

Racial and Ethnic Disparities in Outcomes After Breast-Conserving Therapy and Endocrine Therapy for DCIS: A Post-Hoc Analysis of the NSABP B-35 Randomized Clinical Trial.

Racial and ethnic disparities in outcomes after treatment for ductal carcinoma in situ (DCIS) are largely unknown. The objective of this study was to examine breast cancer outcomes by race and ethnicity in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-35 clinical trial. The NSABP B-35 trial randomized postmenopausal women with hormone receptor-positive DCIS treated with breast-conserving therapy to 5 years of tamoxifen or anastrozole. In total, 3104 women were enrolled between 2003 and 2006. For this analysis, patients without complete self-reported race and ethnicity or with immediate trial dropout were excluded. Kaplan-Meier curves and adjusted Cox-proportional hazards models were used for analyses. Of the 3061 women included, 2614 (85.4%) were non-Hispanic white (NHW), 255 (8.3%) were non-Hispanic Black (NHB), 95 (3.1%) were Hispanic, and 96 (3.1%) were Asian or Pacific Islander (API). Endocrine therapy assignment and duration were well balanced between racial and ethnic groups. Median follow-up was 9 years; unadjusted Kaplan-Meier curves did not show any racial differences in disease events. Adjusted Cox-proportional hazards models found API (versus NHW) race to be associated with higher local recurrence [hazard ratio (HzR) 2.45, p = 0.035] and NHB race to be associated with higher distant recurrence (HzR 5.03, p = 0.020) and breast cancer mortality (HzR 3.83, p = 0.046). Despite similar locoregional treatments and standard endocrine therapy in a clinical trial population, racial and ethnic disparities exist in long-term outcomes for hormone-receptor-positive DCIS. These findings suggest that factors outside of access and treatment may impact DCIS outcomes by race and ethnicity.

Gene Expression and Benefit of Chemotherapy in Women With Node-Negative, Estrogen Receptor–Positive Breast Cancer

PURPOSE The 21-gene recurrence score (RS) assay quantifies the likelihood of distant recurrence in women with estrogen receptor–positive, lymph node–negative breast cancer treated with adjuvant tamoxifen. The relationship between the RS and chemotherapy benefit is not known. METHODS The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy–treated patients in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B20 trial. Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS. RESULTS A total of 651 patients were assessable (227 randomly assigned to tamoxifen and 424 randomly assigned to tamoxifen plus chemotherapy). The test for interaction between chemotherapy treatment and RS was statistically significant ( P = .038). Patients with high-RS (≥ 31) tumors (ie, high risk of recurrence) had a large benefit from chemotherapy (relative risk, 0.26; 95% CI, 0.13 to 0.53; absolute decrease in 10-year distant recurrence rate: mean, 27.6%; SE, 8.0%). Patients with low-RS (< 18) tumors derived minimal, if any, benefit from chemotherapy treatment (relative risk, 1.31; 95% CI, 0.46 to 3.78; absolute decrease in distant recurrence rate at 10 years: mean, −1.1%; SE, 2.2%). Patients with intermediate-RS tumors did not appear to have a large benefit, but the uncertainty in the estimate can not exclude a clinically important benefit. CONCLUSION The RS assay not only quantifies the likelihood of breast cancer recurrence in women with node-negative, estrogen receptor–positive breast cancer, but also predicts the magnitude of chemotherapy benefit.

Flashback Foreword: Preoperative Therapy for Operable Breast Cancer and Clinical Features of Triple-Negative Breast Cancer

Article Tools FLASHBACK FOREWORD Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. March 29, 2023 Response to Neoadjuvant Therapy and Long-Term Survival in Patients With Triple-Negative Breast Cancer. March 29, 2023 ARTICLE CITATION DOI: 10.1200/JCO.22.02784 Journal of Clinical Oncology - published online before print March 29, 2023 PMID: 36989608 Flashback Foreword: Preoperative Therapy for Operable Breast Cancer and Clinical Features of Triple-Negative Breast Cancer Clifford A. Hudis , MD1,2xClifford A. HudisSearch for articles by this author Show More 1Former Associate Editor, Journal of Clinical Oncology, Alexandria, VA2American Society of Clinical Oncology, Alexandria, VA https://doi.org/10.1200/JCO.22.02784 First Page Full Text PDF Figures and Tables © 2023 by American Society of Clinical OncologyTHE TAKEAWAYIn 1998, with the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18, Fisher et al1 demonstrated that preoperative (earlier) use of conventional postoperative adjuvant therapy did not improve or diminish overall outcomes (disease-free and overall survival) in early-stage breast cancer. In 2008, Liedtke et al2 suggested that response (specifically failure to achieve a pathologic complete response) after preoperative therapy could identify those patients with poor prognosis triple-negative disease who would have worse long-term outcomes. The impact of these studies today is that we can offer preoperative therapy where it is needed knowing it is safe and effective, and we can use this setting to help accelerate the pace of research.AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTFlashback Foreword: Preoperative Therapy for Operable Breast Cancer and Clinical Features of Triple-Negative Breast CancerThe following represents disclosure information provided by the author of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).Clifford A. HudisUncompensated Relationships: Alliance Foundation Trials, Columbia University, Memorial Sloan-Kettering Cancer CenterOpen Payments Link: https://openpaymentsdata.cms.gov/physician/471974No other potential conflicts of interest were reported. Companion Effect of preoperative chemotherapy on the outcome of women with operable breast cancer Response to Neoadjuvant Therapy and Long-Term Survival in Patients With Triple-Negative Breast Cancer

Effect of preoperative chemotherapy on the outcome of women with operable breast cancer.

To determine, in women with primary operable breast cancer, if preoperative doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan; AC) therapy yields a better outcome than postoperative AC therapy, if a relationship exists between outcome and tumor response to preoperative chemotherapy, and if such therapy results in the performance of more lumpectomies. Women (1,523) enrolled onto National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 were randomly assigned to preoperative or postoperative AC therapy. Clinical tumor response to preoperative therapy was graded as complete (cCR), partial (cPR), or no response (cNR). Tumors with a cCR were further categorized as either pathologic complete response (pCR) or invasive cells (pINV). Disease-free survival (DFS), distant disease-free survival (DDFS), and survival were estimated through 5 years and compared between treatment groups. In the preoperative arm, proportional-hazards models were used to investigate the relationship between outcome and tumor response. There was no significant difference in DFS, DDFS, or survival (P = .99, .70, and .83, respectively) among patients in either group. More patients treated preoperatively than postoperatively underwent lumpectomy and radiation therapy (67.8% v 59.8%, respectively). Rates of ipsilateral breast tumor recurrence (IBTR) after lumpectomy were similar in both groups (7.9% and 5.8%, respectively; P = .23). Outcome was better in women whose tumors showed a pCR than in those with a pINV, cPR, or cNR (relapse-free survival [RFS] rates, 85.7%, 76.9%, 68.1%, and 63.9%, respectively; P < .0001), even when baseline prognostic variables were controlled. When prognostic models were compared for each treatment group, the preoperative model, which included breast tumor response as a variable, discriminated outcome among patients to about the same degree as the postoperative model. Preoperative chemotherapy is as effective as postoperative chemotherapy, permits more lumpectomies, is appropriate for the treatment of certain patients with stages I and II disease, and can be used to study breast cancer biology. Tumor response to preoperative chemotherapy correlates with outcome and could be a surrogate for evaluating the effect of chemotherapy on micrometastases; however, knowledge of such a response provided little prognostic information beyond that which resulted from postoperative therapy.

Combinational chemotherapy for the treatment of colon cancer

The second leading cause of cancer-related death is colon cancer. Combination chemotherapy can lessen the chance of re-occurrence and demise due to recurred or illness that has spread in patients who have had curative surgery. According to the findings of the Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) and the National Surgical Adjuvant Breast and Bowel Project (NSABP) C-07 trials, combination regimens that include fluoropyrimidine and oxaliplatin are the current standard of care. Targeted medicines for combination adjuvant treatment in the second and third stages of colon cancer are an assuring area, there is no proof to support its use in this situation at this stage. Postoperative therapy has a well-established role in the elderly population, though the most appropriate regimen is still to be established. Improved surgical and radiotherapy techniques may help the patients achieve better results. Further studies should be undertaken in order to determine patient subgroups prone to recurrence, predict response to therapy, and develop better treatment strategies for individuals with colon cancer

Racial disparity in distant recurrence-free survival in patients with localized breast cancer: A pooled analysis of National Surgical Adjuvant Breast and Bowel Project trials.

Black race is associated with worse outcome in patients with breast cancer. The distant relapse-free survival (DRFS) between Black and White women with localized breast cancer who participated in National Cancer Institute-sponsored clinical trial was evaluated. Pooled data were analyzed from 8 National Surgical Adjuvant Breast and Bowel Project (NSABP) trials including 9702 women with localized breast cancer treated with adjuvant chemotherapy (AC, n = 7485) or neoadjuvant chemotherapy (NAC, n = 2217), who self-reported as Black (n = 1070) or White (n = 8632) race. The association between race and DRFS was analyzed using log-rank tests and multivariate Cox regression. After adjustment for covariates including age, tumor size, nodal status, body mass index and taxane use, and treatment (AC vs NAC), Black race was associated with an inferior DRFS in estrogen receptor-positive (ER+; hazard ratio [HR], 1.24; 95% CI, 1.05-1.46; P = .01), but not in ER- disease (HR, 0.97; 95% CI, 0.83-1.14; P = .73), and significant interaction between race and ER status was observed (P = .03). There was no racial disparity in DRFS among patients with pathologic complete response (pCR) (log-rank P = .8). For patients without pCR, Black race was associated with worse DRFS in ER+ (HR, 1.67; 95% CI, 1.14-2.45; P = .01), but not in ER- disease (HR, 0.91; 95% CI, 0.65-1.28; P = .59). Black race was associated with significantly inferior DRFS in ER+ localized breast cancer treated with AC or NAC, but not in ER- disease. In the NAC group, racial disparity was also observed in patients with residual ER+ breast cancer at surgery, but not in those who had pCR. Black women with breast cancer have worse outcomes compared with White women. We investigated if this held true in the context of clinical trials that provide controlled treatment setting. Black women with cancer expressing estrogen receptors (ERs) had worse outcome than White women. If breast cancers did not express ERs, there was no racial disparity in outcome. We also observed racial disparity in women who received chemotherapy before their cancer was removed, but only if they had cancer expressing ERs and residual disease on completion of treatment. If the cancer disappeared with presurgical chemotherapy, there was no racial disparity.

Evaluating Regional Nodal Irradiation Allocation and Association with Oncologic Outcomes in NSABP B-18, B-27, B-40, and B-41

There is a lack of level I evidence to guide radiation therapy recommendations for patients receiving neoadjuvant chemotherapy for breast cancer. We used 4 neoadjuvant chemotherapy trials to determine which patients benefit from regional nodal irradiation (RNI). We obtained data from the NSABP (National Surgical Adjuvant Breast and Bowel Project) B-18, B-27, B-40, and B-41 clinical trials. B-40 and B-41 allowed RNI at physician's discretion. We evaluated locoregional recurrence (LRR), distant recurrence, disease-free survival, and overall survival (OS). Kaplan-Meier, Peto-Peto, χ2, Fisher exact, and Wilcoxon rank-sum tests were used for survival estimates and comparison. Median follow-up for B-18, B-27, B-40, and B-41 was 13.7, 9.7, 4.5, and 5.1 years, respectively, including 742, 2254, 1154, and 504 patients for analysis. On multivariable analysis, factors significantly associated with RNI included tumor size, ypN status, and tumor subtype; Hispanic patients were less likely to receive RNI. Patients with ypN+HER2+ disease who received RNI had improved OS. B-40 patients with ypN+HR+ disease had improved LRR. On multivariable analysis for the B-40 and B-41 study population, RNI was not associated with significantly improved OS, disease-free survival, distant recurrence, or LRR. RNI was associated with a clinical benefit for patients with ypN+HER2+ and ypN+HR+ disease. RNI was not significantly associated with a clinically beneficial outcome for the entire cohort. Prospective phase 3 clinical trials are needed to establish guidelines for patients who should receive RNI after neoadjuvant treatment, and action is necessary to eliminate the disparity in care delivery shown for Hispanic women.

A Short History of Bernard Fisher's Contributions to Randomized Clinical Trials.

Dr. Bernard Fisher (1918-2019) was an early proponent of evidence-based medicine using the mechanism of prospective, multicenter, randomized clinical trials to test biological and clinical hypotheses. In this article, I trace how his early scientific work in striving to understand the nature of cancer metastasis through animal experiments led to a new, testable, clinical hypothesis: that surgery to remove only the tumor and a small amount of tissue around it was as effective as the more disfiguring operations that were then the standard treatment. Fisher's work with the National Surgical Adjuvant Breast and Bowel Project (NSABP) using large, randomized clinical trials to demonstrate the veracity of this hypothesis led to a new paradigm in which the emphasis was placed on how systemic therapies used at an early stage of disease could effectively eradicate breast cancer for many patients. This new therapeutic approach led to the successful development of new treatments, many of which are widely used today. Ultimately, the new paradigm led to successfully preventing breast cancer in women who were at high risk for the disease but who had not yet been diagnosed with the disease. Throughout his entire career, Fisher championed the use of large prospective, randomized clinical trials despite criticism from many in the medical community who strongly criticized his use of randomization as a mechanism for testing clinical hypotheses. The approach he and the NSABP employed is still considered to be the highest standard of evidence in conducting clinical studies.

Joseph R. Bertino: In Memoriam (1930–2021)

Joseph R. Bertino: In Memoriam (1930–2021)

The influence of preoperative biopsy on the surgical method in breast cancer patients: a single-center experience of 3,966 cases in China.

The National Surgical Adjuvant Breast and Bowel Project (NSABP) B32 trial reported that the detection rate of sentinel lymph nodes by core needle biopsy (CNB) is higher than that by segmental resection. However, there are few reports regarding the detection rate of sentinel lymph nodes by vacuum-assisted breast biopsy (VABB). Therefore, we analyzed the impact of preoperative biopsy methods on the surgical modes of 3,966 patients with breast cancer in our center. In total, 3,966 female breast cancer patients [clinical tumor node metastasis (TNM) stage I-III] were enrolled in this study. Preoperative pathological diagnosis methods included fine needle aspiration (FNA) biopsy, CNB, excision biopsy, and VABB. According to the time of diagnosis. The data were analysis by chi square test, variance analysis and the Kaplan-Meier time series in SPSS 22.0. There was a decrease in the number of patients that underwent excision biopsy (7.3% to 2.7%) and intraoperative freezing (89.4% to 28.9%) over time, while CNB exhibited an increasing trend (1.6% to 55.3%). The positive rates of VABB, CNB, excision biopsy, and FNA were 99.5%, 97.1%, 97.9%, and 82.2%, respectively, and the false negative rates were 0%, 1.8%, 0.34%, and 8.9%, respectively. The overall breast-conserving rate was 36.7%, while the breast-conserving rate for VABB was 57.1%. The axillary sentinel lymph node biopsy rate of cN0 patients was 48.3%, and the intraoperative frozen group (36.7%) and excision biopsy group (39.5%) were lower than the CNB (57.1%) and VABB (77.9%) groups. Until December 2019, there were 350 cases with tumor recurrence or metastasis. The methods of biopsy were not correlated to the cumulative survival time. Changes to the diagnosis and treatment of breast cancer has a profound impact on the method of tumor biopsy. VABB biopsy offers advantages such as accurate diagnosis, a greater volume of tissue taken at one time, minimally invasive and repeatable, and does not affect the surgical approach and prognosis of patients. It will gradually become the primary method of preoperative pathological evaluation of breast cancer.

Antimullerian Hormone as a Serum Biomarker for Risk of Chemotherapy-Induced Amenorrhea.

Antimullerian hormone (AMH) is a promising biomarker for ovarian reserve. In this study, we assessed AMH before and 1 year after initiation of adjuvant chemotherapy onNational Surgical Adjuvant Breast and Bowel Project (NSABP)/NRG Oncology B-47 in female participants aged 42 years and younger (median age = 39 years). At baseline, median AMH was 1.2 ng/mL; 13 (4.7%) values were less than 0.1 ng/mL (the threshold for detectable levels, in the perimenopause and menopause range), and 57 values (20.6%) were less than 0.5 ng/mL. At 1 year, 215 (77.6%) were less than 0.1 ng/mL, and 264 (95.3%) were less than 0.5 ng/mL. Postchemotherapy menses were reported by 46.2% of participants. Multivariable logistic regression found that the odds of having postchemotherapy menses increased with younger age, higher body mass index, and higher prechemotherapy AMH, but not by trastuzumab administration or by the choice of chemotherapy (doxorubicin-cyclophosphamide followed by paclitaxel vs docetaxel-cyclophosphamide). We conclude that higher prechemotherapy AMH predicts a lower risk of chemotherapy-induced amenorrhea and that AMH 1 year after chemotherapy initiation is not informative in this setting because it is likely to be very low.

Inference on quantile residual life for length-biased survival data

Length biased data occurs when a prevalent sampling is used to recruit subject into a study that investigates the time from an initial event to a terminal event. Such data are usually left-truncated and right-censored. While there have been accurate and efficient methods to estimate the survival function, not much work have been done regarding estimation of residual life time distribution or the summary parameters such as the median and quantiles of the residual life. In this paper we propose two ways to estimate the quantiles of the residual life time at fixed time points accounting for the length biased and censored na- ture of the data. We provide the asymptotic properties of these estimators and investigate them through simulation studies. Considering that the variance of these estimators require density estimation, we suggest an alternate approach to obtain the confidence intervals for the residual function. We apply these methods to a breast cancer dataset from National Surgical Adjuvant Breast and Bowel Project (NSABP).

Bernard Fisher: US surgeon who pioneered a scientific approach for breast cancer treatment

Credit: Archives of Bernard Fisher The US surgeon Bernard Fisher has died at the age of 101. As chairman of the National Surgical Adjuvant Breast and Bowel Project (NSABP) he...

Partial-Breast Irradiation: Review of Modern Trials

Following partial mastectomy, whole-breast irradiation (WBI), delivered over 3 to 6 weeks, has been the standard adjuvant radiation approach for early-stage breast cancer. A growing body of literature over the past decade has suggested that irradiation of the partial breast, including the tumor bed plus a margin, may be a suitable alternative for appropriately selected patients. The use of partial breast irradiation (PBI) has been studied in multiple prospective randomized trials, now with up to 10 years of follow-up, establishing similar safety and efficacy compared with WBI. Advantages of PBI include (1) reduced treatment duration, (2) potential reductions in treatment-related toxicity, (3) improved cosmetic outcomes, and (4) reduced costs. The purpose of this article is to review appropriate patient selection criteria, clinical and toxicity outcomes data, clinical consensus practice guidelines, and the various PBI techniques. The National Surgical Adjuvant Breast and Bowel Project (NSABP) B39/Radiation Therapy Oncology Group (RTOG) 0413 study (NRG Oncology) is the most recently published (abstract form only) prospective randomized trial comparing PBI using 3D conformal external beam radiation therapy (3D-CRT, 38.5 Gy/10 fractions, twice daily) or brachytherapy (interstitial catheters or applicator based, 34 Gy/10 fractions, twice daily), vs. WBI (50 Gy ± tumor a bed boost). With a median follow-up of 10.2 years, the 10-year ipsilateral breast tumor recurrence-free interval was 95.2% vs. 95.9% for PBI and WBI, although it did not meet the statistical significance for equivalence. Similarly, the randomized trial of accelerated partial breast irradiation using 3-dimensional conformal radiotherapy (RAPID) trial is a prospective randomized trial comparing primarily 3D-CRT (38.5 Gy/10 fractions, twice daily) with WBI, (42.5 Gy/16 daily fractions or 50 Gy/25 daily fractions ± tumor bed boost). Rates of ipsilateral breast tumor recurrence (IBTR) at 8 years were not statistically significantly different (PBI vs WBI, 3% vs. 2.8%; HR = 1.27; 90% VI, 0.84–1.91). There is a growing body of literature supporting the use of PBI in appropriately selected patients and its use should continue to increase.

BMI is an independent prognostic factor for late outcome in patients diagnosed with early breast cancer: A landmark survival analysis

BMI is an independent prognostic factor for late outcome in patients diagnosed with early breast cancer: A landmark survival analysis

Abstract P4-10-04: Assessment of clinical trial participation on breast cancer survival

Abstract Background Accredited cancer treatment centers offer clinical trials for patients since it is universally accepted that participation in these trials is advantageous. Purpose The purpose of this study was to assess whether clinical trial participation was associated with a survival advantage. Methods We identified 308,291 cases of first primary female invasive breast cancer from the California Cancer Registry 2000-2015. Participation in a clinical trial was documented. Clinical trials were defined as National Cancer Institute (NCI) sponsored studies such as National Surgical Adjuvant Breast and Bowel Project (NSABP) and Southwest Oncology Group (SWOG); pharmaceutical trials; and local investigator initiated studies. The distribution of age, race/ethnicity, socioeconomic status (SES), and stage between clinical trial participants and non-participants was compared using contingency tables and the χ2 Test. Kaplan-Meier Survival Analysis and the Log Rank test were used to compare differences in breast cancer specific survival between participants and non-participants. Cox Regression Analysis was used to estimate the risk of mortality between participants and non-participants after adjusting for age, race/ethnicity, SES, grade, and treatment. Analyses were conducted separately for each stage. Hazard ratios (HR) and 95% confidence intervals (CIs) were reported. Results There were 3,517 (1.1%) patients who participated in a clinical trial. Almost 50% of participants were enrolled in an NCI trial, 38% in a local/investigator initiated study, and 13% were in a trial sponsored by a pharmaceutical company. Trial participation was highest for patients less than 45 years of age (21.9%) and lowest in patients 70 years of age and older (12.3%). Most participants were in stage 2 (44.6%). Participation increased with increasing SES. Only 8.5% of participants were in the lowest SES whereas 35.4% were in the highest SES. Unadjusted survival analysis indicated that there was no survival advantage for stage 1 patients (χ2 = 0.41, p=0.52) whereas study participants in stages 2, 3, and 4 had statistically significantly better survival. Adjusted hazard ratios indicated that stage 2 patients participating in a trial had a 23% reduced risk of mortality (HR=0.77; CI: 0.65 - 0.94). For patients in stage 4, the risk of mortality was reduced by 36% (HR=0.64; CI: 0.47 - 0.87). There was no risk reduction for patients in stages 1 and 3. Conclusion Only a small percent of patients enroll in breast cancer clinical trials and participation is correlated with age and SES. There is a survival advantage for participation in a clinical trial for stages 2 and 4 patients. Citation Format: Parise C, Caggiano V. Assessment of clinical trial participation on breast cancer survival [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-10-04.

Pathological Assessment of Response to Neoadjuvant Chemotherapy among Carcinoma Breast Patients in a Tertiary Level Hospital

Background: The role of the pathologist reporting a case of post-chemotherapy carcinoma breast involves not just looking for residual carcinoma, but also classifying the patient into a response category, based on histological findings, and thus, analyzing the efficacy of treatment. Therapy related changes are well described in carcinoma breast. This study aims at classifying post-chemotherapy specimens based on response to chemotherapy according to the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 system and also identifying important associations between morphology, lymph node metastases and hormone receptor status with response. Methods: The study classified thirty-one cases of carcinoma breast who had undergone neoadjuvant chemotherapy in our institution into three categories based on the NSABP B18 system, and analyzed the association of changes in morphology, hormone receptor status and metastases to lymph nodes with presence or absence of response. Results: The commonest response category was partial response (pPR) (17 cases), followed by pathological non-response (pNR) (11 cases) and pathological complete response (pCR) (3 cases). Statistically significant associations were found between presence of residual mass on gross assessment and presence of lymph node metastases with a poor response to treatment. Histopathological features and change in hormone receptor status did not show a significant association with response. Conclusion: The majority of patients showed a partial response to therapy. Presence of a residual mass and presence of metastases to lymph nodes signified poor response.

Three-Fraction Intracavitary Accelerated Partial Breast Brachytherapy: Early Provider and Patient-Reported Outcomes of a Novel Regimen

To report early adverse events and patient-reported outcomes (PROs) of 3-fraction intracavitary catheter-based partial breast brachytherapy (ICBB). Eligible women ≥50years of age with ≤2.5-cm, lymph node-negative invasive or in situ breast cancer underwent breast-conserving surgery and placement of a brachytherapy applicator. ICBB was initiated on the second weekday after surgery and prescribed to 21Gy in 3 once-daily fractions. Common Terminology Criteria for Adverse Events, version 4.0; 10-point linear analog scale assessment; the PRO version of the Common Terminology Criteria for Adverse Events; and the Harvard Breast Cosmesis Scale were used for provider and patient-reported assessments. Seventy-three women were treated for invasive (79%) or in situ (21%) breast cancer. The median time to completion of surgery and radiation therapy was 6days. After 14-months median follow-up, 2 patients (3%) had developed breast infections that resolved with oral antibiotics. There was no other treatment-associated adverse event grade ≥2. The grade 1 seroma rate at 3months was 20%, which dropped to 8% at 12months; no events required intervention. At 12months, 91% of patients reported an overall quality of life score as ≥8 of 10, and patient-reported cosmesis was good or excellent in 95%. All patients are alive without relapse at the last follow-up. Three-fraction ICBB is associated with low rates of early provider and patient- reported adverse events and compares favorably with early outcomes of more protracted ICBB regimens, including twice-daily (3.4Gy×10) fractionation studied in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39. Further investigation is warranted.

Indications for and efficacy of postmastectomy radiotherapy for patients with a favorable response to neoadjuvant chemotherapy.

Prospective, randomized data regarding the use of postmastectomy radiotherapy (PMRT) in women who receive neoadjuvant chemotherapy (NAC) are lacking. The usefulness of PMRT in patients who respond well to NAC forms the basis of the ongoing National Surgical Adjuvant Breast and Bowel Project (NSABP) B51/Radiation Therapy Oncology Group (RTOG) 0413 clinical trial. Herein, the authors review the current literature examining the role of PMRT in women who receive NAC prior to surgery.