Publications by authors named "Tari King"

171 Publications

Utility of the 21-Gene Recurrence Score in Node-Positive Breast Cancer.

Oncology (Williston Park) 2021 Feb 11;35(2):77-84. Epub 2021 Feb 11.

Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA.

The 21-gene Recurrence Score (RS) assay has been validated as both a prognostic and predictive tool in node-negative (pN0), estrogen receptor-positive (ER+), HER2-negative (HER2-) breast cancer. A large body of evidence supports the clinical utility of the RS in the node positive (pN+) population as well. Retrospective analyses of archived tissue from multiple clinical trials have found the RS to be prognostic in both endocrine therapy (ET)-treated and chemotherapy-treated patient with pN+ disease. Distribution of RS results in pN+ patients have also been consistent with those of pN0 populations. Data from the SWOG 8814 trial and large population-based registries further support the prognostic and potential predictive value of the RS. Specifically, patients with 1 to 3 positive nodes and RS less than 18 derived negligible benefit from adjuvant chemotherapy in these studies. In the prospective West German Study Group PlanB and ADAPT trials, pN+ patients with RS less than 11 and RS 25 or less, respectively, who were treated with ET alone experienced excellent outcomes. Finally, 5-year results of the RxPONDER clinical trial randomizing patients with 1 to 3 positive nodes and RS 25 or less to ET alone vs ET plus chemotherapy confirmed an absence of chemotherapy benefit in postmenopausal patients. Clinical practice guidelines support use of the RS in the pN+, ER+/HER2- population, and many institutions have adopted the RS to guide clinical decisionmaking, resulting in a net reduction of adjuvant chemotherapy use. This review highlights the existing data supporting the prognostic and predictive ability of the RS in pN+ disease, current practice patterns related to RS use in this population, and emerging applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.46883/ONC.2021.3502.0077DOI Listing
February 2021

Prediction of Persistent Pain Severity and Impact 12 Months After Breast Surgery Using Comprehensive Preoperative Assessment of Biopsychosocial Pain Modulators.

Ann Surg Oncol 2021 Jan 15. Epub 2021 Jan 15.

Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Background: Persistent post-mastectomy pain (PPMP) is a significant negative outcome occurring after breast surgery, and understanding which individual women are most at risk is essential to targeting of preventive efforts. The biopsychosocial model of pain suggests that factors from many domains may importantly modulate pain processing and predict the progression to pain persistence.

Methods: This prospective longitudinal observational cohort study used detailed and comprehensive psychosocial and psychophysical assessment to characterize individual pain-processing phenotypes in 259 women preoperatively. Pain severity and functional impact then were longitudinally assessed using both validated surgery-specific and general pain questionnaires to survey patients who underwent lumpectomy, mastectomy, or mastectomy with reconstruction in the first postsurgical year. An agnostic, multivariable modeling strategy identified consistent predictors of several pain outcomes at 12 months.

Results: The preoperative characteristics most consistently associated with PPMP outcomes were preexisting surgical area pain, less education, increased somatization, and baseline sleep disturbance, with axillary dissection emerging as the only consistent surgical variable to predict worse pain. Greater pain catastrophizing, negative affect, younger age, higher body mass index (BMI), and chemotherapy also were independently predictive of pain impact, but not severity. Sensory disturbance in the surgical area was predicted by a slightly different subset of factors, including higher preoperative temporal summation of pain.

Conclusions: This comprehensive approach assessing consistent predictors of pain severity, functional impact, and sensory disturbance may inform personalized prevention of PPMP and also may allow stratification and enrichment in future preventive studies of women at higher risk of this outcome, including pharmacologic and behavioral interventions and regional anesthesia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-020-09479-2DOI Listing
January 2021

ASO Author Reflections: Tailoring Axillary Surgery After Neoadjuvant Endocrine Therapy for Breast Cancer.

Ann Surg Oncol 2021 Mar 2;28(3):1368-1369. Epub 2021 Jan 2.

Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-020-09435-0DOI Listing
March 2021

Surgical Treatment after Neoadjuvant Systemic Therapy in Young Women with Breast Cancer: Results from a Prospective Cohort Study.

Ann Surg 2020 Dec 23;Publish Ahead of Print. Epub 2020 Dec 23.

Department of Surgery, University of Ulsan, College of Medicine, Asan Medical Center, Seoul, South Korea Dana-Farber Cancer Institute, Boston, MA, USA Brigham and Women's Hospital, Boston, MA, USA Mayo Clinic, Rochester, MN, USA Stanford University, Palo Alto, CA, USA Beth Israel Deaconess Medical Center, Boston, MA, USA Massachusetts General Hospital, Boston, MA, USA University of Colorado Cancer Center, Aurora, CO, USA Sunnybrook Health Sciences Centre, Toronto, Ontario, USA Metrowest Medical Center, Framingham, MA, USA.

Objective: We aimed to investigate eligibility for breast-conserving surgery (BCS) pre- and post-neoadjuvant systemic therapy (NST), and trends in the surgical treatment of young breast cancer patients.

Background: Young women with breast cancer are more likely to present with larger tumors and aggressive phenotypes, and may benefit from NST. Little is known about how response to NAC influences surgical decisions in young women.

Methods: The Young Women's Breast Cancer Study (YWS), a multicenter prospective cohort of women diagnosed with breast cancer at age ≤40, enrolled 1302 patients from 2006 to 2016. Disease characteristics, surgical recommendations, and reasons for choosing mastectomy among BCS-eligible patients were obtained through the medical record. Trends in use of NST, rate of clinical and pathologic complete response (cCR and pCR), and surgery were also assessed.

Results: Of 1117 women with unilateral stage I-III breast cancer, 315 (28%) received NST. Pre-NST, 26% were BCS eligible, 17% were borderline eligible, and 55% were ineligible. After NST, BCS eligibility increased from 26% to 42% (p < 0.0001). Among BCS-eligible patients after NST (n = 133), 41% chose mastectomy with reasons being patient preference (53%), BRCA or TP53 mutation (35%) and family history (5%). From 2006 to 2016, the rates of NST (p = 0.0012), cCR (p < 0.0001) and bilateral mastectomy (p < 0.0001) increased, but the rate of BCS did not increase (p = 0.34).

Conclusion: While the proportion of young women eligible for BCS increased after NST, many patients choose mastectomy, suggesting that surgical decisions are often driven by factors beyond extent of disease and treatment response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000004296DOI Listing
December 2020

Contemporary Multi-Institutional Cohort of 550 Cases of Phyllodes Tumors (2007-2017) Demonstrates a Need for More Individualized Margin Guidelines.

J Clin Oncol 2021 Jan 10;39(3):178-189. Epub 2020 Dec 10.

Department of Surgery, Mayo Clinic, Rochester, MN.

Purpose: Phyllodes tumors (PTs) are rare breast neoplasms, which have little granular data on margins. Current guidelines recommend ≥ 1 cm margins; however, recent data suggest narrower margins are sufficient, and for benign PT, a negative margin may not be necessary.

Methods: We performed an 11-institution contemporary (2007-2017) review of PT practices. Demographics, surgical, and histopathologic data were captured. Logistic regression was used to estimate the association of select covariates with local recurrence (LR).

Results: Of 550 PT patients, the majority underwent excisional biopsy (55.3%, n = 302/546) or lumpectomy (wide excision) (38.5%, n = 210/546). Median tumor size was 30 mm, 68.9% (n = 379) were benign, 19.6% (n = 108) borderline, and 10.5% (n = 58) malignant. Surgical margins were positive in 42% (n = 231) and negative in 57.3% (n = 311). A second operation was performed in 38.0% (n = 209) of the total cohort, including 51 patients with an initial margin (82.4% with < 2 mm), and 157 with an initial margin, with residual disease only found in six (2.9%). Notably, 32.0% (n = 74) of those with an initial positive margin did undergo a second operation, among whom only 2.7% (n = 2) recurred. Recurrence occurred in 3.3% (n = 18) of the total cohort (n = 15 LR, n = 3 distant), at median follow-up of 36.7 months. LR (all PT grades) was not reduced with wider negative margin width (≥ 2 mm < 2 mm: odds ratio [OR] = 0.39; 95% CI, 0.07 to 2.10; = .27) or final margin status (positive negative: OR = 0.96; 95% CI, 0.26 to 3.52; = .96).

Conclusion: In current practice, many patients are managed outside of current guidelines. For the entire cohort, a wider margin width was not associated with a reduced risk of LR. We do not recommend re-excision of a negative margin for benign PT, regardless of margin width, as a progressively wider surgical margin is unlikely to reduce LR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.20.02647DOI Listing
January 2021

American Society of Clinical Oncology Road to Recovery Report: Learning From the COVID-19 Experience to Improve Clinical Research and Cancer Care.

J Clin Oncol 2021 01 8;39(2):155-169. Epub 2020 Dec 8.

Sarah Cannon, Nashville, TN.

This report presents the American Society of Clinical Oncology's (ASCO's) evaluation of the adaptations in care delivery, research operations, and regulatory oversight made in response to the coronavirus pandemic and presents recommendations for moving forward as the pandemic recedes. ASCO organized its recommendations for clinical research around five goals to ensure lessons learned from the COVID-19 experience are used to craft a more equitable, accessible, and efficient clinical research system that protects patient safety, ensures scientific integrity, and maintains data quality. The specific goals are: (1) ensure that clinical research is accessible, affordable, and equitable; (2) design more pragmatic and efficient clinical trials; (3) minimize administrative and regulatory burdens on research sites; (4) recruit, retain, and support a well-trained clinical research workforce; and (5) promote appropriate oversight and review of clinical trial conduct and results. Similarly, ASCO also organized its recommendations regarding cancer care delivery around five goals: (1) promote and protect equitable access to high-quality cancer care; (2) support safe delivery of high-quality cancer care; (3) advance policies to ensure oncology providers have sufficient resources to provide high-quality patient care; (4) recognize and address threats to clinician, provider, and patient well-being; and (5) improve patient access to high-quality cancer care via telemedicine. ASCO will work at all levels to advance the recommendations made in this report.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.20.02953DOI Listing
January 2021

Tumor phenotype and concordance in synchronous bilateral breast cancer in young women.

Breast Cancer Res Treat 2021 Apr 26;186(3):815-821. Epub 2020 Nov 26.

Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA.

Purpose: Synchronous bilateral breast cancer is uncommon, and its pattern and incidence among younger women is unknown. Here we report the incidence, phenotypes, and long-term oncologic outcomes of bilateral breast cancer in women enrolled in the Young Women's Breast Cancer Study (YWS).

Methods: The YWS is a multi-center, prospective cohort study of women with breast cancer diagnosed at age ≤ 40 years. Those with synchronous bilateral breast cancer formed our study cohort. Tumor phenotypes were categorized as luminal A (hormone receptor (HR)+/HER2-/grade 1/2), luminal B (HR+ /HER2+ or HER2- and grade 3), HER2-enriched (HR-/HER2+), or basal-like (HR-/HER2-). Descriptive statistics were used to evaluate tumor phenotypes of bilateral cancers for concordance.

Results: Among 1302 patients enrolled in the YWS, 21 (1.6%) patients had synchronous bilateral disease. The median age of diagnosis was 38 years (range 18-40 years). Seventeen (81.0%) underwent genetic testing with 6 found to have pathogenic germline mutations in BRCA1, BRCA2, or TP53. The majority of patients (76.2%) underwent bilateral mastectomy. On pathology, 2 patients had bilateral in-situ disease, 6 had unilateral invasive and contralateral in-situ disease, and 13 had bilateral invasive disease. Of those with bilateral invasive disease, 10 (76.9%) had bilateral luminal tumors and, when fully characterized, 6 were of the same luminal subtype. Only 1 patient had bilateral basal-like breast cancer. At median follow-up of 8.2 years, 14 patients are alive with no recurrent disease.

Conclusions: Bilateral breast cancer is uncommon among young women diagnosed with breast cancer at age ≤ 40. In our cohort, the majority of invasive tumors were of the luminal phenotype, though some differed by grade or HER2 status. These findings support the need for thorough pathologic workup of bilateral disease when it is found in young women with breast cancer to determine risk and tailor treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10549-020-06027-0DOI Listing
April 2021

Clinico-pathologic predictors of patterns of residual disease following neoadjuvant chemotherapy for breast cancer.

Mod Pathol 2020 Nov 20. Epub 2020 Nov 20.

Breast Oncology Program, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA.

Among breast cancer patients treated with neoadjuvant chemotherapy (NAC) who do not experience a pathologic complete response (pCR), the pattern of residual disease in the breast varies. Pre-treatment clinico-pathologic features that predict the pattern of residual tumor are not well established. To investigate this issue, we performed a detailed review of histologic sections of the post-treatment surgical specimens for 665 patients with stage I-III breast cancer treated with NAC followed by surgery from 2004 to 2014 and for whom slides of the post-NAC surgical specimen were available for review. This included 242 (36.4%) patients with hormone receptor (HR)+/HER2- cancers, 216 (32.5%) with HER2+ tumors, and 207 (31.1%) with triple negative breast cancer (TNBC). Slide review was blinded to pre-treatment clinico-pathologic features. pCR was achieved in 7.9%, 37.0%, and 37.7%, of HR+/HER2- cancers, HER2+ cancers, and TNBC respectively (p < 0.001). Among 389 patients with residual invasive cancer in whom the pattern of residual disease could be assessed, 287 (73.8%) had a scattered pattern and 102 (26.2%) had a circumscribed pattern. In both univariate and multivariate analyses, there was a significant association between tumor subtype and pattern of response. Among patients with HR+/HER2- tumors, 89.4% had a scattered pattern and only 10.6% had a circumscribed pattern. In contrast, among those with TNBC 52.8% had a circumscribed pattern and 47.2% had a scattered pattern (p < 0.001). In addition to subtype, histologic grade and tumor size at presentation were also significantly related to the pattern of residual disease in multivariate analysis, with lower grade and larger size each associated with a scattered response pattern (p = 0.002 and p = 0.01, respectively). A better understanding of the relationship between pre-treatment clinico-pathologic features of the tumor and pattern of residual disease may be of value for helping to guide post-chemotherapy surgical management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41379-020-00714-5DOI Listing
November 2020

Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Guideline Update.

J Clin Oncol 2021 Feb 20;39(6):685-693. Epub 2020 Oct 20.

The University of Texas MD Anderson Cancer Center, Houston, TX.

Purpose: The aim of this work is to update key recommendations of the ASCO guideline adaptation of the Cancer Care Ontario guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer and adjuvant targeted therapy for breast cancer.

Methods: An Expert Panel conducted a targeted systematic literature review guided by a signals approach to identify new, potentially practice-changing data that might translate into revised guideline recommendations.

Results: The Expert Panel reviewed abstracts from the literature review and identified one article for inclusion that reported results of the phase III, open-label KATHERINE trial. In the KATHERINE trial, patients with stage I to III human epidermal growth factor receptor 2 (HER2)-positive breast cancer with residual invasive disease in the breast or axilla after completing neoadjuvant chemotherapy and HER2-targeted therapy were allocated to adjuvant trastuzumab emtansine (T-DM1; n = 743) or to trastuzumab (n = 743). Invasive disease-free survival was significantly higher in the T-DM1 group than in the trastuzumab arm (hazard ratio, 0.50; 95% CI, 0.39 to 0.64; < .001), and risk of distant recurrence was lower in patients who received T-DM1 than in patients who received trastuzumab (hazard ratio, 0.60; 95% CI, 0.45 to 0.79). Grade 3 or higher adverse events occurred in 190 patients (25.7%) who received T-DM1 and in 111 patients (15.4%) who received trastuzumab.

Recommendations: Patients with HER2-positive breast cancer with pathologic invasive residual disease at surgery after standard preoperative chemotherapy and HER2-targeted therapy should be offered 14 cycles of adjuvant T-DM1, unless there is disease recurrence or unmanageable toxicity. Clinicians may offer any of the available and approved formulations of trastuzumab, including trastuzumab, trastuzumab and hyaluronidase-oysk, and available biosimilars.Additional information can be found at www.asco.org/breast-cancer-guidelines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.20.02510DOI Listing
February 2021

Strategies to Optimize Axillary Surgery in Patients With Breast Cancer Receiving Neoadjuvant Endocrine Therapy.

Oncology (Williston Park) 2020 Oct;34(10):397-404

Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA.

Current guidelines for axillary surgery following systemic therapy do not differentiate between neoadjuvant endocrine therapy (NET) and neoadjuvant chemotherapy (NAC). Without specific guidelines, many assume that axillary surgery after NET should mirror that after NAC; however, NET has traditionally been used for patients with biologically favorable disease, so alternative axillary surgery strategies may be appropriate. Unfortunately, clinical trials that have examined NET have not rigorously studied axillary management or outcomes. The limited observational data available reveal that axillary lymph node dissection (ALND) is less frequently performed for positive nodes following NET than NAC; ALND rates after NET are more like those of upfront surgery patients. Although outcomes of omitting ALND after NET in patients who remain node positive are unknown, hypothesis-generating work from the National Cancer Database suggests that most patients selected for NET have limited nodal burden, and the prognostic significance of residual nodal disease after NET may not carry the same implications as residual disease after NAC. As such, there is opportunity to define axillary surgery strategies after NET that differ from those used after NAC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.46883/ONC.2020.3410.0397DOI Listing
October 2020

The Incidence of Adjacent Synchronous Invasive Carcinoma and/or Ductal Carcinoma In Situ in Patients with Intraductal Papilloma without Atypia on Core Biopsy: Results from a Prospective Multi-Institutional Registry (TBCRC 034).

Ann Surg Oncol 2020 Oct 12. Epub 2020 Oct 12.

Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.

Background: Available retrospective data suggest the upgrade rate for intraductal papilloma (IP) without atypia on core biopsy (CB) ranges from 0 to 12%, leading to variation in recommendations. We conducted a prospective multi-institutional trial (TBCRC 034) to determine the upgrade rate to invasive cancer (IC) or ductal carcinoma in situ (DCIS) at excision for asymptomatic IP without atypia on CB.

Methods: Prospectively identified patients with a CB diagnosis of IP who had consented to excision were included. Discordant cases, including BI-RADS > 4, and those with additional lesions requiring excision were excluded. The primary endpoint was upgrade to IC or DCIS by local pathology review with a predefined rule that an upgrade rate of ≤ 3% would not warrant routine excision. Sample size and confidence intervals were based on exact binomial calculations. Secondary endpoints included diagnostic concordance for IP between local and central pathology review and upgrade rates by central pathology review.

Results: The trial included116 patients (median age 56 years, range 24-82) and the most common imaging abnormality was a mass (n = 91, 78%). Per local review, 2 (1.7%) cases were upgraded to DCIS. In both of these cases central pathology review did not confirm DCIS on excision. Additionally, central pathology review confirmed IP without atypia in core biopsies of 85/116 cases (73%), and both locally upgraded cases were among them.

Conclusion: In this prospective study of 116 IPs without atypia on CB, the upgrade rate was 1.7% by local review, suggesting that routine excision is not indicated for IP without atypia on CB with concordant imaging findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-020-09215-wDOI Listing
October 2020

Multidisciplinary considerations in the treatment of triple-negative breast cancer.

CA Cancer J Clin 2020 Nov 28;70(6):432-442. Epub 2020 Sep 28.

Breast Oncology Program, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3322/caac.21643DOI Listing
November 2020

Oncotype DX testing in node-positive breast cancer strongly impacts chemotherapy use at a comprehensive cancer center.

Breast Cancer Res Treat 2021 Jan 16;185(1):215-227. Epub 2020 Sep 16.

Breast Oncology Program, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA.

Purpose: In 2016, we initiated standardized "reflex" Oncotype DX Recurrence Score (RS) testing for patients ≤ 65 years with pT1-2N0-1 HR/HER2 breast cancer. Here, we examine RS testing patterns, RS distribution, and factors associated with chemotherapy use in patients with pN1 breast cancer.

Methods: Patients with stage I-III HR/HER2 pN1 breast cancer treated with upfront surgery from February 2016 to March 2019 were identified. Clinical characteristics were compared between patients meeting reflex RS testing criteria, those with RS ordered outside of reflex criteria, and those without RS testing. RS was categorized as low (< 18), intermediate (18-30), and high (≥ 31). Multivariate logistic regression was performed to identify factors associated with adjuvant chemotherapy receipt. We examined 3-year recurrence-free survival (RFS) and overall survival (OS) stratified by chemotherapy use.

Results: We identified 347 HR/HER2 pN1 patients; 272 (78.4%) received RS testing, and 194 (71.3%) met reflex criteria. RS was < 18 in 164 (61.4%) patients, 18-30 in 89 (32.7%) patients, and ≥ 31 in 16 (5.9%) patients. On multivariate analysis, RS < 18 (OR 0.47, 95% CI 0.24-0.92) was associated with lower odds of chemotherapy use, whereas presence of lymphovascular invasion (OR 1.77, 95% CI 1.03-3.07) and lobular subtype (OR 2.40, 95% CI 1.21-4.78) were associated with higher odds. No differences in 3-year RFS (p = 0.97) or OS (p = 0.19) based on chemotherapy receipt were observed.

Conclusion: Most RS-tested HR/HER2 pN1 patients at our center had low genomic risk. A low RS independently influenced chemotherapy omission and in RS-tested patients, short-term outcomes were excellent. Our study demonstrates increased use of RS in guiding adjuvant treatment decisions in node-positive disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10549-020-05931-9DOI Listing
January 2021

Axillary Management After Neoadjuvant Endocrine Therapy for Hormone Receptor-Positive Breast Cancer.

Ann Surg Oncol 2021 Mar 31;28(3):1358-1367. Epub 2020 Aug 31.

Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.

Background: Data to guide axillary management after neoadjuvant endocrine therapy (NET) remain limited.

Methods: We analyzed type of axillary surgery [sentinel lymph node biopsy (SLNB) vs. axillary lymph node dissection (ALND)] and residual nodal disease burden after NET in two cohorts of patients with cT1-4N0-1M0 hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer: Dana-Farber/Brigham and Women's Cancer Center (DFBWCC) cohort (2015-2018) and the National Cancer Data Base (NCDB) cohort (2012-2016). Cox proportional hazard regression was used to determine adjusted 5-year overall survival (OS) by type of axillary surgery.

Results: Ninety-four (4.3%) of 2191 HR+/HER2- DFBWCC patients and 4363 (1.5%) of 283,344 NCDB patients were selected for NET. Of those who underwent axillary surgery, 30 (43.5%) in the DFBWCC cohort and 1583 (40.6%) in the NCDB cohort had ALND. Over 90% of cN0 patients in both cohorts had fewer than three positive nodes on final pathology [44 (95.7%) DFBWCC and 2945 (91.3%) NCDB]. In contrast, only 7 (30.4%) DFBWCC patients and 342 (50.7%) NCDB cN1 patients had fewer than three positive nodes. In the DFBWCC patients, there were no locoregional recurrences and four distant recurrences. In the NCDB, 5-year OS did not differ by type of axillary surgery regardless of residual nodal disease burden: 96.6% SLNB versus 97.9% ALND for 0 positive nodes; 84.4% versus 84.4% for one to two positive nodes, and 75.9% versus 77.3% for three or more positive nodes (all p > 0.10).

Conclusions: In cN0 patients selected for NET, > 90% have fewer than three positive nodes at surgery. The lack of a survival difference between SLNB and ALND suggests an opportunity to de-escalate treatment of the axilla in patients with limited residual nodal disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-020-09073-6DOI Listing
March 2021

Reply to Comment on Margins in Breast-Conserving Surgery After Neoadjuvant Therapy.

Authors:
Tari A King

Ann Surg Oncol 2020 Aug 30. Epub 2020 Aug 30.

Associate Chair for Multidisciplinary Oncology, Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-020-09088-zDOI Listing
August 2020

Prognostic significance of residual nodal disease after neoadjuvant endocrine therapy for hormone receptor-positive breast cancer.

NPJ Breast Cancer 2020 13;6:35. Epub 2020 Aug 13.

Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA USA.

Axillary management after NET has not been well studied and the significance of residual axillary node disease after NET remains uncertain. We used the National Cancer Data Base to examine the prognostic significance of residual nodal disease after NET. From 2010-2016, 4,496 patients received NET for cT1-3N0-1M0 hormone receptor-positive, HER2-negative breast cancer. Among cN0 patients treated with NET, final node status was ypN0 in 65%, isolated tumor cells (ITCs) in 3%, ypN1mi in 6%, and ypN1 in 26%. In cN1 patients, nodal pathologic complete response was uncommon (10%), and residual nodal disease included ITCs in 1%, ypN1mi in 3%, and ypN1 in 86%. There were no differences in 5-year overall survival (OS) between patients with pathologic node-negative disease, ITCs, or micrometastases after NET. When compared to a matched cohort of upfront surgery patients, there were also no differences in 5-year OS between NET and upfront surgery patients for any residual nodal disease category. These findings suggest NET patient outcomes mirror those of upfront surgery patients and present an opportunity to consider de-escalation of axillary management strategies in NET patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41523-020-00177-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426953PMC
August 2020

Association Between Time to Operation and Pathologic Stage in Ductal Carcinoma in Situ and Early-Stage Hormone Receptor-Positive Breast Cancer.

J Am Coll Surg 2020 10 6;231(4):434-447.e2. Epub 2020 Aug 6.

Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, and Breast Oncology Program, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA. Electronic address:

Background: During the COVID-19 pandemic, surgical delays have been common for patients with ductal carcinoma in situ (DCIS) and early-stage estrogen receptor-positive (ER+) breast cancer, often in favor of neoadjuvant endocrine therapy (NET). To understand possible ramifications of these delays, we examined the association between time to operation and pathologic staging and overall survival (OS).

Study Design: Patients with DCIS or ER+ cT1-2N0 breast cancer treated from 2010 through 2016 were identified in the National Cancer Database. Time to operation was recorded. Factors associated with pathologic upstaging were examined using logistic regression analyses. Cox proportional hazard models were used to analyze OS. Analyses were stratified by disease stage and initial treatment strategy.

Results: There were 378,839 patients identified. Among those undergoing primary surgical procedure, time to operation was within 120 days in > 98% in all groups. Among cT1-2N0 patients selected for NET, operations were performed within 120 days in 59.6% of cT1N0 and 30.9% of cT2N0 patients. Increased time to operation was associated with increased odds of pathologic upstaging in DCIS patients (ER+: 60 to 120 days: odds ratio 1.15; 95% CI, 1.08 to 1.22; more than 120 days: odds ratio 1.44; 95% CI, 1.24 to 1.68; ER-: 60 to 120 days: NS; more than 120 days: odds ratio 1.36; 95% CI, 1.01 to 1.82; 60 days or less: reference), but not in patients with invasive cancer, irrespective of initial treatment strategy. No difference in OS was seen by time to operation in DCIS or NET patients.

Conclusions: Increased time to operation was associated with a small increase in pathologic upstaging in DCIS patients, but did not impact OS. In patients with cT1-2N0 disease, NET use did not impact stage or OS, supporting the safety of delay strategies in ER+ breast cancer patients during the pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jamcollsurg.2020.06.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409804PMC
October 2020

Patient preferences for locoregional therapy in early-stage breast cancer.

Breast Cancer Res Treat 2020 Sep 20;183(2):291-309. Epub 2020 Jul 20.

Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, 450 Brookline Ave, Yawkey 12, Boston, MA, 02215, USA.

Purpose: With an increasing emphasis on patient-centered care, clinicians in subspecialties such as breast surgery and radiation oncology that offer multiple therapeutic options with equivalent outcomes are under increasing pressure to aid patients with the decision-making process. The aim of this review is to summarize existing studies that either evaluated factors in patient's decision-making regarding locoregional therapy in early-stage breast cancer or evaluated benefit thresholds required to change therapy decisions.

Methods: A PubMed search to identify prospective or retrospective studies written in English reporting factors in patient decision-making regarding locoregional therapy in early-stage breast cancer was conducted. No restriction was placed on publication date. Studies that focused on breast reconstruction decisions or on patient preferences for decision-making involvement were excluded.

Results: A total of 39 studies were identified; 19 examining patient preferences for breast-conserving surgery versus mastectomy, 7 on preferences for contralateral prophylactic mastectomy, 2 on non-surgical options, 2 on the extent of axillary surgery, and 9 on radiation therapy decisions. Themes such as fear of recurrence, desire to avoid additional invasive therapy, and the importance of physician preference were common, but many studies also highlighted factors important to specific subpopulations of women.

Conclusions: Patient preference is difficult to define and measure, and heterogeneity across studies renders direct comparison difficult. Future work is needed to define women's risk-thresholds for certain treatments, delve into the psychological factors that direct their decisions, and understand how patients' valuations of risk interact with society's.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10549-020-05737-9DOI Listing
September 2020

The Landmark Series: Neoadjuvant Endocrine Therapy for Breast Cancer.

Ann Surg Oncol 2020 Sep 26;27(9):3393-3401. Epub 2020 Jun 26.

Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.

Patients with estrogen receptor (ER)-positive breast cancer generally do not have significant response to neoadjuvant chemotherapy. In these patients, neoadjuvant endocrine therapy (NET) is an alternative for those who may benefit from tumor downsizing prior to surgery. This article reviews clinical trials that have defined the role of NET. Cumulatively, these trials demonstrate that NET is effective in downsizing ER-positive breast tumors. Aromatase inhibitors are preferred in postmenopausal patients. An aromatase inhibitor with ovarian suppression is effective in premenopausal patients. While trials to date have shown the effectiveness of NET to facilitate breast conservation, they have provided little data regarding optimal axillary management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-020-08530-6DOI Listing
September 2020

Weathering the Storm: Managing Older Adults With Breast Cancer Amid COVID-19 and Beyond.

J Natl Cancer Inst 2021 Apr;113(4):355-359

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Caring for older patients with breast cancer presents unique clinical considerations because of preexisting and competing comorbidity, the potential for treatment-related toxicity, and the consequent impact on functional status. In the context of the COVID-19 pandemic, treatment decision making for older patients is especially challenging and encourages us to refocus our treatment priorities. While we work to avoid treatment delays and maintain therapeutic benefit, we also need to minimize the risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposures, myelosuppression, general chemotherapy toxicity, and functional decline. Herein, we propose multidisciplinary care considerations for the aging patient with breast cancer, with the goal to promote a team-based, multidisciplinary treatment approach during the COVID-19 pandemic and beyond. These considerations remain relevant as we navigate the "new normal" for the approximately 30% of breast cancer patients aged 70 years and older who are diagnosed in the United States annually and for the thousands of older patients living with recurrent and/or metastatic disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jnci/djaa079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313961PMC
April 2021

Regional Nodal Management in Patients With Clinically Node-Negative Breast Cancer Undergoing Upfront Surgery.

J Clin Oncol 2020 07 22;38(20):2273-2280. Epub 2020 May 22.

Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.19.02891DOI Listing
July 2020

Optimizing Radiation Therapy to Boost Systemic Immune Responses in Breast Cancer: A Critical Review for Breast Radiation Oncologists.

Int J Radiat Oncol Biol Phys 2020 09 14;108(1):227-241. Epub 2020 May 14.

Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Immunotherapy using immune checkpoint blockade has revolutionized the treatment of many types of cancer. Radiation therapy (RT)-particularly when delivered at high doses using newer techniques-may be capable of generating systemic antitumor effects when combined with immunotherapy in breast cancer. These systemic effects might be due to the local immune-priming effects of RT resulting in the expansion and circulation of effector immune cells to distant sites. Although this concept merits further exploration, several challenges need to be overcome. One is an understanding of how the heterogeneity of breast cancers may relate to tumor immunogenicity. Another concerns the need to develop knowledge and expertise in delivery, sequencing, and timing of RT with immunotherapy. Clinical trials addressing these issues are under way. We here review and discuss the particular opportunities and issues regarding this topic, including the design of informative clinical and translational studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2020.05.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646202PMC
September 2020

Insulin resistance contributes to racial disparities in breast cancer prognosis in US women.

Breast Cancer Res 2020 05 12;22(1):40. Epub 2020 May 12.

Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: Racial disparities in breast cancer survival between Black and White women persist across all stages of breast cancer. The metabolic syndrome (MetS) of insulin resistance disproportionately affects more Black than White women. It has not been discerned if insulin resistance mediates the link between race and poor prognosis in breast cancer. We aimed to determine whether insulin resistance mediates in part the association between race and breast cancer prognosis, and if insulin receptor (IR) and insulin-like growth factor receptor (IGF-1R) expression differs between tumors from Black and White women.

Methods: We conducted a cross-sectional, multi-center study across ten hospitals. Self-identified Black women and White women with newly diagnosed invasive breast cancer were recruited. The primary outcome was to determine if insulin resistance, which was calculated using the homeostatic model assessment of insulin resistance (HOMA-IR), mediated the effect of race on prognosis using the multivariate linear mediation model. Demographic data, anthropometric measurements, and fasting blood were collected. Poor prognosis was defined as a Nottingham Prognostic Index (NPI) > 4.4. Breast cancer pathology specimens were evaluated for IR and IGF-1R expression by immunohistochemistry (IHC).

Results: Five hundred fifteen women were recruited (83% White, 17% Black). The MetS was more prevalent in Black women than in White women (40% vs 20%, p < 0.0001). HOMA-IR was higher in Black women than in White women (1.9 ± 1.2 vs 1.3 ± 1.4, p = 0.0005). Poor breast cancer prognosis was more prevalent in Black women than in White women (28% vs 15%. p = 0.004). HOMA-IR was positively associated with NPI score (r = 0.1, p = 0.02). The mediation model, adjusted for age, revealed that HOMA-IR significantly mediated the association between Black race and poor prognosis (β = 0.04, 95% CI 0.005-0.009, p = 0.002). IR expression was higher in tumors from Black women than in those from White women (79% vs 52%, p = 0.004), and greater IR/IGF-1R ratio was also associated with higher NPI score (IR/IGF-1R >  1: 4.2 ± 0.8 vs IR/IGF-1R = 1: 3.9 ± 0.8 vs IR/IGF-1R < 1: 3.5 ± 1.0, p < 0.0001).

Conclusions: In this multi-center, cross-sectional study of US women with newly diagnosed invasive breast cancer, insulin resistance is one factor mediating part of the association between race and poor prognosis in breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13058-020-01281-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216707PMC
May 2020

American Registry of Pathology Expert Opinions: The Spectrum of Lobular Carcinoma in Situ: Diagnostic Features and Clinical Implications.

Ann Diagn Pathol 2020 Apr 15;45:151481. Epub 2020 Feb 15.

University of Queensland and Pathology Queensland, Royal Brisbane and Women's Hospital, Herston, Australia.

This review reflects a collaboration between the American Registry of Pathology (the publisher of the Armed Forces Institute of Pathology Fascicles) and Annals of Diagnostic Pathology. It is part of a series of expert recommendations on topics encountered in daily practice. The authors, 4 pathologists with expertise in breast pathology and a breast surgeon with a clinical and research interest in lobular carcinoma in situ (LCIS), met by conference call in September 2019 to develop recommendations for evaluating and reporting LCIS. Herein, we summarize the diagnostic criteria of classic LCIS and LCIS subtypes according to the most recent WHO criteria, discuss how best to distinguish LCIS from ductal carcinoma in situ in problematic cases (including the uses and limitations of E-cadherin immunohistochemistry), and review outcome and management issues for patients with LCIS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anndiagpath.2020.151481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401835PMC
April 2020

Development and Validation of the BREAST-Q Breast-Conserving Therapy Module.

Ann Surg Oncol 2020 Jul 21;27(7):2238-2247. Epub 2020 Jan 21.

Division of Plastic and Reconstructive Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Background: In breast cancer surgery, patient-reported outcome measures are needed to measure outcomes best reported by patients (e.g., psychosocial well-being). This study aimed to develop and validate a new BREAST-Q module to address the unique concerns of patients undergoing breast-conserving therapy (BCT).

Methods: Phase 1 involved qualitative and cognitive interviews with women who had BCT and clinical expert input to establish content for the BCT module. A field-test (phase 2) was performed, and Rasch measurement theory (RMT) analysis was used for item reduction and examination of reliability and validity. Validation of the item-reduced scales in a clinical sample (phase 3) was conducted for further assessment of their psychometric properties.

Results: Qualitative interviews with 24 women resulted in the addition of 15 new items across multiple existing BREAST-Q scales and the development of two new scales (Adverse Effects of Radiation and Satisfaction With Information-Radiation Therapy). Feedback from 15 patients and 5 clinical experts were used to refine the instructions, response options, and item wording. An RMT analysis of data from 3497 women resulted in item reduction. The final set of scales showed evidence of ordered response option thresholds, good item fit, and good reliability, except for the Adverse Effects of the Radiation Scale. Validity and reliability were further supported by the phase 3 data from 3125 women.

Conclusions: The BREAST-Q BCT module can be used in research and clinical care to evaluate quality metrics and to compare surgical outcomes across all breast cancer surgery patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-019-08195-wDOI Listing
July 2020

Extent of axillary surgery in inflammatory breast cancer: a survival analysis of 3500 patients.

Breast Cancer Res Treat 2020 Feb 20;180(1):207-217. Epub 2020 Jan 20.

Department of Surgery, Duke University Medical Center, Box 3513, Durham, NC, 27710, USA.

Purpose: Inflammatory breast cancer (IBC) is an aggressive variant for which axillary lymph node (LN) dissection following neoadjuvant chemotherapy (NACT) remains standard of care. But with increasingly effective systemic therapy, it is unclear whether more limited axillary surgery may be appropriate in some IBC patients. We sought to examine whether extent of axillary LN surgery was associated with overall survival (OS) for IBC.

Methods: Female breast cancer patients with non-metastatic IBC (cT4d) diagnosed 2010-2014 were identified in the National Cancer Data Base. Cox proportional hazards modeling was used to estimate the association between extent of axillary surgery (≤ 9 vs ≥ 10 LNs removed) and OS after adjusting for covariates, including post-NACT nodal status (ypN0 vs ypN1-3) and radiotherapy receipt (yes/no).

Results: 3471 patients were included: 597 (17.2%) had cN0 disease, 1833 (52.8%) had cN1 disease, and 1041 (30%) had cN2-3 disease. 49.9% of cN0 patients were confirmed to be ypN0 on post-NACT surgical pathology. Being ypN0 (vs ypN1-3) was associated with improved adjusted OS for all patients. Radiotherapy was associated with improved adjusted OS for cN1 and cN2-3 patients but not for cN0 patients. Regardless of ypN status, there was a trend towards improved adjusted OS with having ≥ 10 (vs ≤ 9) LNs removed for cN2-3 patients (HR 0.78, 95% CI 0.60-1.01, p = 0.06) but not for cN0 patients (p = 0.83).

Conclusions: A majority of IBC patients in our study presented with node-positive disease, and for those presenting with cN2-3 disease, more extensive axillary surgery is potentially associated with improved survival. For cN0 patients, however, more extensive axillary surgery was not associated with a survival benefit, suggesting an opportunity for more personalized care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10549-020-05529-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050768PMC
February 2020

Genomic profiling of pleomorphic and florid lobular carcinoma in situ reveals highly recurrent ERBB2 and ERRB3 alterations.

Mod Pathol 2020 07 13;33(7):1287-1297. Epub 2020 Jan 13.

Division of Breast Surgery, Brigham and Women's Hospital, Boston, MA, USA.

Pleomorphic LCIS (P-LCIS) and florid LCIS (F-LCIS) are morphologic variants distinguished from classic LCIS by marked nuclear pleomorphism and/or an expansile growth pattern with or without necrosis. Given the rarity of these LCIS variants, little data exist regarding their molecular pathogenesis, natural history, and optimal management. The purpose of this study was to genomically profile LCIS variants to gain further insight into their biology. Nineteen cases of pure LCIS variants (17 P-LCIS, 2 F-LCIS) diagnosed on core needle biopsy at our institution from 2006 to 2017 were included, five of which were upgraded to invasive cancer at excision. Macrodissected lesions were analyzed by a hybrid-capture next generation sequencing assay that surveyed exonic sequences of 447 genes for mutations and copy number variations (CNVs) and 191 regions across 60 genes for structural rearrangements. LCIS variants were all confirmed as E-cadherin negative by immunohistochemistry. Receptor profiles among the 17 P-LCIS cases included HR+/HER2- (nine cases), HR+/HER2+ (three cases), HR-/HER2+ (two cases), and HR-/HER2- (three cases). The two F-LCIS cases were HR+/HER2- and HR+/HER2+. All LCIS variants had genetic alterations consistent with a lobular phenotype including 1q gain (16 cases), 16q loss (18 cases), and CDH1 mutations (18 cases). Highly recurrent ERBB2 alterations were noted including mutations (13 cases) and amplifications (six cases). Other significant alterations included mutations in PIK3CA (six cases), RUNX1 (four cases), ERBB3 (four cases), and CBFB (three cases), as well as amplification of CCND1 (five cases). A TP53 mutation was identified in one case of HR-/HER2+ P-LCIS with signet ring cell features that lacked 1q gain and 16q loss. P-LCIS and F-LCIS contain genetic alterations characteristic of lobular neoplasia; however, these LCIS variants are distinguished from classical LCIS reported in the literature by their highly recurrent ERBB2 alterations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41379-020-0459-6DOI Listing
July 2020

The Association of Modifiable Breast Cancer Risk Factors and Somatic Genomic Alterations in Breast Tumors: The Cancer Genome Atlas Network.

Cancer Epidemiol Biomarkers Prev 2020 03 13;29(3):599-605. Epub 2020 Jan 13.

Channing Division of Network Medicine, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts.

Background: The link between modifiable breast cancer risk factors and tumor genomic alterations remains largely unexplored. We evaluated the association of prediagnostic body mass index (BMI), cigarette smoking, and alcohol consumption with somatic copy number variation (SCNV), total somatic mutation burden (TSMB), seven single base substitution (SBS) signatures (SBS1, SBS2, SBS3, SBS5, SBS13, SBS29, and SBS30), and nine driver mutations (, and ) in a subset of The Cancer Genome Atlas (TCGA).

Methods: Clinical and genomic data were retrieved from the TCGA database. Risk factor information was collected from four TCGA sites ( = 219 women), including BMI (1 year before diagnosis), cigarette smoking (smokers/nonsmokers), and alcohol consumption (current drinkers/nondrinkers). Multivariable regression analyses were conducted in all tumors and stratified according to estrogen receptor (ER) status.

Results: Increasing BMI was associated with increasing SCNV in all women ( = 0.039) and among women with ER tumors ( = 0.031). Smokers had higher SCNV and TSMB versus nonsmokers ( < 0.05 all women). Alcohol drinkers had higher SCNV versus nondrinkers ( < 0.05 all women and among women with ER tumors). SBS3 (defective homologous recombination-based repair) was exclusively found in alcohol drinkers with ER disease. mutation was more likely to occur in women with higher BMI. No association was significant after multiple testing correction.

Conclusions: This study provides preliminary evidence that BMI, cigarette smoking, and alcohol consumption can influence breast tumor biology, in particular, DNA alterations.

Impact: This study demonstrates a link between modifiable breast cancer risk factors and tumor genomic alterations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1055-9965.EPI-19-1087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060119PMC
March 2020

Association Between 21-Gene Assay Recurrence Score and Locoregional Recurrence Rates in Patients With Node-Positive Breast Cancer.

JAMA Oncol 2020 04;6(4):505-511

Department of Medicine, Division of Hematology/Oncology, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois.

Importance: The 21-gene assay recurrence score is increasingly used to personalize treatment recommendations for systemic therapy in postmenopausal women with estrogen receptor (ER)- or progesterone receptor (PR)-positive, node-positive breast cancer; however, the relevance of the 21-gene assay to radiotherapy decisions remains uncertain.

Objective: To examine the association between recurrence score and locoregional recurrence (LRR) in a postmenopausal patient population treated with adjuvant chemotherapy followed by tamoxifen or tamoxifen alone.

Design, Setting, And Participants: This cohort study was a retrospective analysis of the Southwest Oncology Group S8814, a phase 3 randomized clinical trial of postmenopausal women with ER/PR-positive, node-positive breast cancer treated with tamoxifen alone, chemotherapy followed by tamoxifen, or concurrent tamoxifen and chemotherapy. Patients at North American clinical centers were enrolled from June 1989 to July 1995. Medical records from patients with recurrence score information were reviewed for LRR and radiotherapy use. Primary analysis included 316 patients and excluded 37 who received both mastectomy and radiotherapy, 9 who received breast-conserving surgery without documented radiotherapy, and 5 with unknown surgical type. All analyses were performed from January 22, 2016, to August 9, 2019.

Main Outcomes And Measures: The LRR was defined as a recurrence in the breast; chest wall; or axillary, infraclavicular, supraclavicular, or internal mammary lymph nodes. Time to LRR was tested with log-rank tests and Cox proportional hazards regression for multivariate models.

Results: The final cohort of this study comprised 316 women with a mean (range) age of 60.4 (44-81) years. Median (interquartile range) follow-up for those without LRR was 8.7 (7.0-10.2) years. Seven LRR events (5.8%) among 121 patients with low recurrence score and 27 LRR events (13.8%) among 195 patients with intermediate or high recurrence score occurred. The estimated 10-year cumulative incidence rates were 9.7% for those with a low recurrence score and 16.5% for the group with intermediate or high recurrence score (P = .02). Among patients who had a mastectomy without radiotherapy (n = 252), the differences in the 10-year actuarial LRR rates remained significant: 7.7 % for the low recurrence score group vs 16.8% for the intermediate or high recurrence score group (P = .03). A multivariable model controlling for randomized treatment, number of positive nodes, and surgical type showed that a higher recurrence score was prognostic for LRR (hazard ratio [HR], 2.36; 95% CI, 1.02-5.45; P = .04). In a subset analysis of patients with a mastectomy and 1 to 3 involved nodes who did not receive radiation therapy, the group with a low recurrence score had a 1.5% rate of LRR, whereas the group with an intermediate or high recurrence score had a 11.1% LRR (P = .051).

Conclusions And Relevance: This study found that higher recurrence scores were associated with increased LRR after adjustment for treatment, type of surgical procedure, and number of positive nodes. This finding suggests that the recurrence score may be used, along with accepted clinical variables, to assess the risk of LRR during radiotherapy decision-making.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaoncol.2019.5559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990911PMC
April 2020

Comparative Analysis of Proposed Strategies for Incorporating Biologic Factors into Breast Cancer Staging.

Ann Surg Oncol 2020 Jul 8;27(7):2229-2237. Epub 2020 Jan 8.

Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: Tumor biology is an important prognostic factor in breast cancer. This study aimed to compare three staging systems incorporating both biologic factors and anatomic staging (AJCC 8th-edition pathologic prognostic staging, Bioscore, and Risk Score) in a large population-based cohort.

Methods: The Surveillance, Epidemiology and End Results program was used to select patients with primary stages 1-4 breast cancer diagnosed in 2010. Patients with inflammatory carcinoma, those with missing data for biologic factors, and those with stages 1-3 disease not treated with surgery were excluded from the study. Estimates of 5-year disease-specific survival (DSS) were calculated using the Kaplan-Meier method. The Harrel concordance index (C-index) and the Akaike Information Criterion were used to compare each model in terms of predicting DSS.

Results: The study included 21,901 patients with a median age of 60 years. The median follow-up period was 52 months. All the staging models stratified DSS, with a stepwise decrease in DSS for each increase in risk category or score. The C-index of each model incorporating biologic factors was higher than the C-index for anatomic staging alone (C-index: 0.832 vs. 0.856 for AJCC pathologic prognostic staging, 0.856 for Bioscore, and 0.864 for Risk Score, all p < 0.001). The staging systems incorporating biologic factors did not differ significantly in terms of model fit.

Conclusion: Staging systems incorporating biologic factors perform better than anatomic staging alone. Implementation of the AJCC 8th-edition pathologic prognostic staging was an important initial step in the inclusion of tumor biology in staging. Given its simplicity and ease of use, the Risk Score should be given consideration as an alternative staging system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-019-08169-yDOI Listing
July 2020