Rate Of Breast-conserving Surgery Research Articles

Regimens of neo-adjuvant chemotherapy in the treatment of breast cancer: A systematic review & network meta-analysis with PRISMA-NMA compliance.

Efficacy of neo-adjuvant therapy depends on the used regimens. There are contradictory findings regarding relative efficacy of these regimens. Accordingly, present study assessed the relative efficacy of Anthracyclines, Taxanes and added targeted therapies in neo-adjuvant setting simultaneously with a focus on tumor response and breast conserving surgery among breast cancer patients. The network meta-analysis model was used. Ranking of treatment was done by surface under cumulative ranking curve for each regimen. Out of 1286 screened records obtained by searching PubMed and Cochrane register of controlled trials, a total of 34 studies randomizing 12,630 breast cancer patients were included. Network meta-analysis for pathological complete response (pCR) revealed Addition of targeted therapies especially Trastuzumab for HER2+ breast cancer and Bevacizumab for HER2- breast cancer along with Anthracyclines and/or Taxanes based chemotherapy significantly improves pCR but with increased haematological toxicities. All the regimens performed similar in terms of breast conserving surgery rates.

Efficacy of neoadjuvant endocrine therapy compared with neoadjuvant chemotherapy in pre-menopausal patients with oestrogen receptor-positive and HER2-negative, lymph node-positive breast cancer

IntroductionNeoadjuvant endocrine therapy (NET) has demonstrated efficacy in post-menopausal patients with hormone-responsive breast cancer. This trial was designed to compare the efficacy of neoadjuvant chemotherapy (NCT) with NET in pre-menopausal breast cancer.Patients and methodsIn this prospective, randomised, phase III study, oestrogen receptor (ER)-positive, HER2-negative, and lymph node-positive pre-menopausal breast cancer patients were recruited from 7 hospitals in South Korea. Enrolled patients were randomly assigned (1:1) to receive 24 weeks of either NCT or NET with goserelin and tamoxifen. The primary purpose was to evaluate the non-inferiority of NET compared to NCT using clinical response, assessed by MRI. Besides, pathological complete response rate (pCR), changes in Ki-67 expression, breast conservation surgery (BCS) rate, and quality of life were included as secondary endpoints.ResultsA total of 187 patients were assigned to receive NCT (n = 95) or NET (n = 92), and 87 patients in each group completed treatments. More NCT patients had complete response or partial response than NET patients using MRI (NCT 83.7% vs. NET 52.9%, 95% CI 17.6–44.0, p < 0.001) and callipers (NCT 83.9% vs. NET 71.3%, 95% CI 0.4–24.9, p = 0.046). Three NCT patients (3.4%) and one NET patient (1.2%) showed pCR (p < 0.005). No difference existed in the conversion rate of BCS (13.8% for NCT vs. 11.5% for NET, p = 0.531) and Ki-67 change (p = 0.114) between the two groups. Nineteen NCT patients had treatment-related grade 3 or worse events compared with none in the NET group.ConclusionsBetter clinical responses were observed in pre-menopausal patients after 24 weeks of NCT compared to those observed after NET.Trial registrationClinicaltrials.gov, NCT01622361. Registration June 19, 2012.

Neoadjuvant chemotherapy versus adjuvant chemotherapy in breast cancer patients: Analysis of breast conserving rate and de-escalation of axillary surgery in 5,141 Korean women.

e12531 Background: Neoadjuvant chemotherapy (NCT) in breast cancer has several advantages such as more breast conservation surgery (BCS) rate and de-escalation of extent of axillary surgery. Actual practice change in this area compared with adjuvant chemotherapy (ACT) is not well established. Methods: We retrospectively analyzed 5,141 women diagnosed with breast cancer from 2009 to 2013, treated with chemotherapy before or after definite surgery. BCS rate and axillary surgery categories (sentinel lymph node biopsy (SNB), axillary lymphnode dissection (ALND) or SNB followed by ALND) are compared between two groups. Results: Among 5,141 patients, 3930 (76.4%) women had ACT and 1211 (23.6%) had NCT. Median age at diagnosis was 48 (range 22-83). BCR rate was lower in T2 (57.1% vs 64.1%), T3 (12.6% vs 20.9%) group between ACT vs NCT ( p=0.03, 0.001), no difference was shown in T1 and T4 tumors. SNB try (SNB only or SNB followed by ALND) rate was still higher in ACT group with cN0 (98.4% vs 95.4%), cN1 (89.3% vs 73.5%), cN2 (77.9% vs 62.1%) tumors ( p=0.001, &lt;0.001, 0.003, respectively). SNB only rate which means that patients spared ALND, was lower in ACT group with all cN stage (cN1; 17.5% vs 29.2%, cN2; 3.2% vs 5.9%, cN3; 5.1% vs 20.5%, all p=0.000) except cN0 (95.6% vs 81.4%, p&lt;0.001). Axillary surgery rate analyzed with pathologic N stage showed more ALNDs attempted even after achieving pathologic complete nodal response or minimal residual N disease (ypN0: 4.4% vs 27.2%, ypN0(i) &amp; ypN1mi; 26.2% vs 57.6%, p&lt;0.001, =0.001 respectively). In contrast however, average of total axillary nodes retrieved by cN stage were statistically lower in NCT group in clinically positive tumors (N1; 15.3 vs 12.7, N2; 19.1 vs 14.6, N3; 25.1 vs 15.6, all p&lt;0.001). Conclusions: NCT had shown advantage to perform more BCS than ACT in T2, T3 tumors. SNB attempts in NCT was comparable to ACT. Still, patients with NCT received more aggressive axillary surgery than ACT shown by axillary surgery category irrespective of negative SNB results.

ALTERNATE: Neoadjuvant endocrine treatment (NET) approaches for clinical stage II or III estrogen receptor-positive HER2-negative breast cancer (ER+ HER2- BC) in postmenopausal (PM) women: Alliance A011106.

504 Background: For PM patients (pts) with locally advanced ER+ HER2- BC, NET improves breast conservation surgery (BCS) rates, and modified preoperative endocrine prognostic index (mPEPI) 0, defined as pT1-2 pN0 Ki67&lt; 2.7%, or pathologic complete response (pCR: no invasive disease in breast or lymph node) is associated with low risk of recurrence without adjuvant chemotherapy (CT). The ALTERNATE trial was initiated to assess if the endocrine-sensitive disease rate (ESDR: number of mPEPI 0 pts/number of eligible pts initiating NET) with fulvestrant (F) or F+anastrozole (A) is improved relative to A alone (reported here) and if the 5-year (yr) recurrence-free survival (RFS) rate for pts with mPEPI 0 on A alone without CT is ≥ 95% (awaits further follow-up). Methods: PM pts with clinical stage II/III ER+ HER2- BC were randomized 1:1:1 to 1 mg A po daily, 500 mg F IM every 4 week (wk)s after loading dose, or A+F for 6 months. Ki67 was tested centrally on biopsies acquired prior to NET, wk 4, wk 12 and at surgery. Pts with Ki67 &gt;10% at wk 4 or 12 were recommended to go off protocol-directed ET and switch to CT. Pts with mPEPI 0 at surgery were recommended to continue assigned ET for 1.5 yrs followed by A for a total of 5 yrs ET (and not to receive CT). The primary endpoint of the neoadjuvant phase was ESDR. ESDR of each F arm was compared to that of the A alone arm. With 425 pts per arm, a one-tailed alpha = 0.025 chi-square test of two independent proportions has 84% power to detect an increase of ≥10% in ESDR for F or F+A compared to the A arm, assuming ESDR ≤30% in A. Results: 1362 pts (A 452; F 454; A+F 456) were enrolled Feb 2014 to Nov 2018. 63 pts were excluded (did not start NET). Of the remaining 1299 pts (A 434; F 431, A+F 434), 42% were cN1-3 and 73% were considered candidates for BCS. ESDR was 18.6% (95%CI: 15.1-22.7%) with A, 22.7% (95%CI: 18.9-27.0%) with F, and 20.5% (95%CI: 16.8-24.6%) with A+F. No significant difference in ESDR was found between A and F (p=0.15) or A and A+F (p=0.55). Among the 825 pts with wk 4 Ki67 &lt; 10% who completed NET and surgery, ESDR and the BCS rate were 27.7% and 70.3% with A; 29.6% and 68.1% with F, and 26.8% and 69.9% with A+F, respectively. Conclusion: Neither F nor F+A significantly improved ESDR compared to A alone in PM pts with locally advanced ER+ HER2- BC. RFS data are awaited. Support: U10CA180821, U10CA180882, U24CA196171, https://acknowledgments.alliancefound.org ; NCI BIQSFP, BCRF, Genentech, AstraZeneca. Clinical trial information: NCT01953588 .

A phase II trial of nivolumab (NIVO) + palbociclib (PAL) + anastrozole (ANA) in postmenopausal women and men with estrogen receptor (ER)+/human epidermal growth factor 2 (HER2)- primary breast cancer (BC): CheckMate 7A8.

TPS1105 Background: Cyclin-dependent kinase 4/6 (CDK 4/6) inhibition coupled with ER signaling blockade is an efficient treatment approach for patients (pts) with metastatic hormone receptor-positive, HER2− BC. Preclinical data suggest synergistic activity of CDK 4/6 inhibition and PD-1 blockade; in a syngeneic mouse tumor model, improved efficacy and complete tumor regression were observed with phased administration of ABE + PD-L1 therapy. Methods: CheckMate 7A8 (NCT04075604) is a randomized, noncomparative, multicenter, phase 2 study evaluating PAL + ANA +/- NIVO in postmenopausal pts with ER+, HER2− primary BC. After determining safe doses for NIVO combination regimens in the safety run-in phase, pts will be randomized in a 4:4:3 ratio to 1 of 3 treatment arms (Table) stratified by PD-L1 expression, node status and tumor size. Following treatment, all pts will undergo surgery and safety follow-up. Eligible pts are postmenopausal women and men with newly diagnosed, untreated, histologically confirmed ER+, HER2− BC with primary tumor ≥ 2 cm; suitable for neoadjuvant endocrine monotherapy and surgery; ECOG PS of 0–1; have baseline tumor tissue available; willing to undergo on-treatment research biopsy and tissue collection at surgery. Primary endpoints are number of pts with occurrence of dose-limiting toxicity (safety run-in phase) and residual cancer burden 0–I rate by central assessment at time of definitive surgery (randomized phase). Secondary endpoints include safety and tolerability, pathologic complete response, objective response rate and breast-conserving surgery rate. Key exploratory endpoints include biomarkers indicative of pharmacodynamic changes and potentially predicting treatment sensitivity. Interim analyses are planned. The study is currently enrolling. Clinical trial information: NCT04075604 . [Table: see text]

Impact of sequence order of anthracyclines and taxanes in neoadjuvant chemotherapy for breast cancer: Results from a prospective institutional database.

e12619 Background: There has been growing interest in the optimal sequencing of anthracyclines and taxanes in neoadjuvant chemotherapy (NACT) for breast cancer. However, data comparing efficacy of administering taxanes prior to anthracyclines as opposed to the opposite sequence remains limited and inconsistent. The objective of our study was to assess the impact of sequence order on pathologic and clinical outcomes in a real-world setting. Methods: A prospective institutional database was analyzed to identify all HER2-negative breast cancer patients treated with NACT from 2012 to 2019. Rates of pathologic complete response (pCR), down-staging, and breast-conserving surgery were compared between patients who received anthracyclines followed by taxanes (AC-T) to those who received taxanes followed by anthracyclines (T-AC). Chi-square and independent sample non-parametric tests were used to test for associations between variables and outcomes. Results: Of the 270 patients who met eligibility criteria, 175 (65%) received AC-T and 95 (35%) received T-AC. Median age was 55 (IQR 24-86). Overall, 83% of patients had stage IIB or greater tumors, 40% had grade 3 histology, and 36% had triple-negative disease. Characteristics were balanced between the AC-T and T-AC groups (all p &lt; 0.05). Median duration of treatment with NACT was 102 days (IQR 29-203). Rates of pCR (19% vs 21%, p = 0.750), down-staging (68% vs 61%, p = 0.188), and conversion to breast-conserving surgery (26% vs 20%, p = 0.314) were similar for AC-T vs T-AC, respectively. pCR was higher in triple-negative compared to hormone-positive cases (33% vs 13%, p &lt; 0.001). Conclusions: In this small population-based cohort, sequence order of anthracyclines and taxanes did not demonstrate statistically significant differences in evaluated outcomes from NACT for breast cancer. This supports the current variation in prescribing practice and highlights the need for further studies in this area.

Current Status and Factors Influencing Surgical Options for Breast Cancer in China: A Nationwide Cross-Sectional Survey of 110 Hospitals.

There are limited nationwide data regarding breast cancer surgery in China. The Chinese Anti-Cancer Association's Committee of Breast Cancer Society and the Chinese Society of Breast Surgeons conducted a nationwide survey to examine the use of and barriers associated with surgical options among patients with breast cancer. Surveys were sent via e-mail to the directors of 110 centers that performed at least 200 breast cancer operations in 2017. The electronic questionnaire contained 183 questions and covered six aspects, including demographic information about the hospitals and surgeons, surgical practice, and application of breast reconstruction. The selected hospitals were from 31 provinces or municipalities. The overall proportion of breast-conserving surgery (BCS) was 22%. Local gross domestic product was significantly related to the rate of BCS (p = .046). Sentinel lymph node biopsy was performed routinely in 76% of hospitals. Only 14.5% (16/110) of hospitals used the dual-tracer method, including radioisotopes. For patients with cN0 disease receiving BCS with one or two positive sentinel lymph nodes, 20% (22/110) of hospitals accepted omitting axillary lymph node dissection (ALND). For patients who underwent mastectomy, only 4% (4/110) of hospitals accepted omitting ALND. There was an obvious polarization trend in the proportion of oncoplastic breast-conserving surgery (OPS); 35/110 (32%) performed OPS in fewer than 10% of cases, whereas 36/110 (33%) performed OPS in more than 50% of cases. OPS was more likely to be performed in academic hospitals. Volume displacement was more commonly used than volume replacement (p < .001). Breast reconstruction was routinely performed in 96/110 (87%) of hospitals, 62% of which involved cooperation with the plastic surgery department. Factors influencing breast reconstruction after mastectomy included the establishment of a plastic surgery department, regional economy, and cooperation between the plastic and general surgery departments. Overall, the proportion of breast reconstruction procedures after mastectomy was 10.7%, with 70% being implant-based reconstruction, 17% autologous tissue reconstruction, and 13% a combination. Overall, 22% of the hospitals predominantly performed immediate breast reconstruction. For delayed reconstruction, two-stage implant-based breast reconstruction was the first choice for 46% of centers, whereas 20% of centers chose autologous reconstruction. Among the 96 centers that performed autologous-based reconstruction, 96% performed latissimus dorsi flap reconstruction, 65% performed transverse rectus abdominis musculocutaneous flap reconstruction, and 45% used deep inferior epigastric artery perforator flaps. The results are of great value for promoting the implementation of a consensus on diagnostic and treatment standards, development of guidelines for breast cancer, and training of breast specialists. This study aimed to establish comprehensive baseline data on the status of current breast cancer treatment in China by presenting the statistics on clinical treatments and surgeries, the distribution of clinical stages, and the demographic characteristics of patients. This report is based on a survey conducted by the Chinese Anti-Cancer Association's Committee of Breast Cancer Society and the Chinese Society of Breast Surgeons, which examined the use of breast cancer surgical options in hospitals all over the country and the factors hindering the adoption of procedures and techniques. This study makes a significant contribution to the literature because there are limited nationwide data regarding breast cancer surgery in China.

The Adoption of Oncoplastic Surgery Using Breast Reduction or Mastopexy Techniques in an Academic Breast Cancer Center Program Can Increase Breast Conservation Rates.

Interest in oncoplastic surgery (OPS), a form of breast conservation surgery (BCS), has grown in the United States over the last decade. Oncoplastic surgery allows for the removal of larger tumors without compromising esthetic outcome or oncologic safety. One of the quality measures on which breast cancer centers in the United States are evaluated is rate of BCS. The purpose of this study was to investigate whether the adoption of OPS increases BCS rates and decreases mastectomy rates at the institutional level. Clinicopathologic data were retrospectively collected for breast cancer patients in a single institution database. Rates of BCS vs mastectomy and partial mastectomy versus OPS were measured between 2012 and 2018 to capture 3 years before and 3 years after the hiring of an oncoplastic surgeon in 2015 with subsequent practice adoption of oncoplastic techniques. We compared the 2 periods using χ and Fisher exact test for categorical variables. Rates of breast conservation and mastectomy were further stratified by tumor stage. Four hundred sixty-eight patients underwent breast cancer surgery at Tufts Medical Center between 2012 and 2018.Patients who underwent surgery between 2012-2015 and 2016-2018 were similar in terms of age, histological type, tumor size, receipt of neoadjuvant therapy, receptor status, and Charlson Comorbidity Index. There was a statistically significant (P < 0.0001) increase in BCS rate after 2015 attributable to the practice adoption of OPS. The proportion of patients who were recommended reexcision did not significantly increase with the introduction of OPS suggesting an appropriate and safe patient selection process for patients undergoing these breast conservation techniques. When stratified by T stage (tumor size), rates of mastectomy for T2 tumors (greater than 2 cm but less than 5 cm) decreased precipitously after 2015 and BCS increased proportionately. The rate of BCS for T1 tumors also increased but less drastically. The adoption of OPS in an academic breast cancer center can result in significantly higher rates of BCS, particularly for those with larger tumors (T2). Academic breast cancer centers should strongly consider incorporating OPS to their treatment paradigm to provide patients with the option to avoid mastectomy.

Surgical Trends in Breast Cancer in Turkey: An Increase in Breast-Conserving Surgery.

PURPOSEBreast cancer is the most frequent cancer in women, and there is a great variability in surgical practice for treating that cancer in different countries. The aims of this study were to analyze the effect of guidelines from the Turkish Federation of Breast Diseases Societies on academic institutions that have breast centers and to evaluate surgical practice in Turkey in 2018.PATIENTS AND METHODSBetween January and March 2019, a survey was sent to breast surgeons who were working in breast centers in academic institutions. The sampling frame included 24 academic institutions with breast centers in 18 cities in Turkey to evaluate interdisciplinary differences among breast centers and seven regions in Turkey regarding patients’ choices, surgical approaches, and academic institutions.RESULTSAll surgeons responded to the survey, and all 4,381 patients were included. Most of the surgeons (73.9%) were working in a breast center. Multidisciplinary tumor boards were performed in 87% of the breast centers. The average time between clinical evaluation and initiation of treatment was 29 days; the longest time was in Southeast Anatolia (66 days). Only 6% of patients had ductal carcinoma in situ. Sentinel lymph node biopsy was available in every region across the country and was performed in 64.5% of the patients. In 2018, the overall breast-conserving surgery rate was 57.3% in Turkey, and it varied from 72.2% in the Black Sea region to 33.5% in Central Anatolia (P < .001). Oncoplastic breast surgery options were available at all breast centers. However, 25% of the breast centers from the Black Sea region and half the breast centers from Eastern Anatolia and the Mediterranean region did not perform this type of surgery.CONCLUSIONIncreasing rates of nonpalpable breast cancer and decreasing rates of locoregional recurrences favored breast-conserving surgery, especially in developed countries. Guidelines from the Turkish Federation of Breast Diseases Societies resulted in more comprehensive breast centers and improved breast health in Turkey.

Abstract P4-13-01: Trends in primary management of invasive lobular carcinoma: An analysis of the National Cancer Database (NCDB)

Abstract Background: Invasive lobular carcinoma (ILC) is typically strongly hormone receptor (HR) positive, with unique characteristics. It has been shown to have poor response to neoadjuvant chemotherapy (NAC) and recent studies describe the benefits of neoadjuvant endocrine therapy (NET). We sought to determine how the primary management strategy in ILC has changed over time, and the impact of ILC tumor biology on its management. Specifically, we hypothesized that use of NAC has decreased, while NET use increased. Additionally, we investigated whether NET is associated with higher rates of breast conservation surgery (BCS) than other primary management strategies. Methods: We queried the NCDB from 2010-2016 and identified all women with ILC who underwent surgical therapy. Patients with stage IV disease were excluded. First course of treatment was classified as: NAC (chemotherapy starting 31-365 days before surgery), NET (short course defined as 7-30 days before surgery; long course defined as 31-365 days before surgery), and primary surgery. Tumors were considered HR+ if they were estrogen receptor and/or progesterone receptor positive. Trends over time in first treatment strategy were compared using Cochrane-Armitage tests. The association between first treatment strategy and use of BCS was assessed using multivariable logistic regression. Results: Among 79,709 women with ILC, 94.0% were HR+/HER2-, 4.7% were HER2+, and 1.3% were triple negative. The most common primary treatment strategy was surgery (92.3%), but the percent undergoing systemic treatment before surgery increased from 7.1% in 2010 to 8.8% in 2016 (p&amp;lt;0.001). The use of NAC increased significantly over the study period in patients with triple negative (12.1% in 2010 to 23.7% in 2016, p=0.007) and HER2+ (12.2% in 2010 to 29.1% in 2016, p&amp;lt;0.001) ILC tumors. Among patients with HR+/HER2- tumors, however, the use of NAC decreased from 4.7% in 2010 to 4.2% in 2016, p=0.007, and the use of long course NET increased significantly, from 1.6% in 2010 to 2.7% in 2016, p&amp;lt;0.001. The use of short course NET in HR+/HER2- patients remained very low over the study period (0.4% in 2010 to 0.5% in 2016, p=0.14). Analyzing the HR+/HER2- subset, 48.4% (295/609) of patients undergoing long course NET with a cT2 tumor underwent BCS compared to 35.3% for primary surgery, 27.3% for NAC, and 24.8% for short course NET (p&amp;lt;0.001). Long course NET was also associated with a higher BCS rate in cT3/cT4 tumors: 22.6% BCS for long course NET, 8.3% BCS for primary surgery, 9.6% BCS for NAC, 7.8% BCS for short course NET (p&amp;lt;0.001). In multivariable analysis including a clinical T category by treatment interaction, long course NET was the only treatment that was associated with higher rates of BCS compared to primary surgery in cT2 (OR 1.51, 95% CI: 1.27-1.79) tumors, while both long course NET (OR 2.52, 95% CI: 1.97-3.22) and NAC (OR 1.54, 95% CI: 1.27-1.88) were associated with increased use of BCS in cT3/cT4 tumors, see Table. Conclusions: The primary management of ILC is slowly evolving over time with a decrease in primary surgery. NAC use has increased appropriately in tumor subtypes with greatest potential benefit (i.e., triple negative or HER2 positive). In HR+/HER2- disease, NAC use has decreased, however NET use has increased and in cT2+ tumors NET was associated with higher rates of BCS. Variable1Odds ratio for BCS (95% CI)p-valueAge, per 1 year increase1.04 (1.03-1.04)&amp;lt;0.001Charlson-Deyo comorbidity score&amp;lt;0.0011 vs 00.86 (0.82-0.90)2+ vs 00.72 (0.66-0.79)Grade2&amp;lt;0.001Moderately/Poorly vsWell Differentiated0.91 (0.88-0.95)Clinical N category2&amp;lt;0.001cN1 vs cN00.49 (0.46-0.52)cN2/cN3 vs cN00.41 (0.35-0.47)Multicentric&amp;lt;0.001Yes vs No0.36 (0.34-0.38)Primary treatment by clinical T category2&amp;lt;0.001For cT1 tumorsLong course NET vs primary surgery0.65 (0.51-0.83)NAC vs Primary surgery0.31 (0.24-0.41)Short course NET vs primary surgery0.85 (0.58-1.24)For cT2 tumorsLong course NET vs primary surgery1.51 (1.27-1.79)NAC vs primary surgery1.04 (0.90-1.20)Short course NET vs primary surgery0.53 (0.33-0.85)For cT3/cT4 tumorsLong course NET vs primary surgery2.52 (1.97-3.22)NAC vs primary surgery1.54 (1.27-1.88)Short course NET vs primary surgery0.79 (0.31-2.02)1Model additionally adjusted for year of diagnosis, race, ethnicity, and insurance status.2Unknown level included in the model but not reported Citation Format: Rita A Mukhtar, Tanya L. Hoskin, Elizabeth B. Habermann, Judy C. Boughey. Trends in primary management of invasive lobular carcinoma: An analysis of the National Cancer Database (NCDB) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-13-01.

Abstract OT2-04-04: Neoadjuvant HER2-targeted therapy +/- immunotherapy with pembrolizumab (neoHIP): An open label randomized phase 2 trial

Abstract Background: Immune checkpoint inhibition (ICI) is synergistic with HER2-directed therapy in pre-clinical models. Clinically, pembrolizumab (K)-mediated ICI plus HER2-directed therapy with trastuzumab (H) was safe and demonstrated modest activity in H-resistant HER2-positive (HER2+) metastatic breast cancer. Because ICI may confer more robust activity when administered earlier in the course of disease, HER2-directed therapy with ICI administered in the curative-intent, treatment-naive setting may allow for de-escalation of cytotoxic backbones; confer life-long, tumor-specific immunity; and ultimately, improve cure rates. Moreover, the synergy of H and K with paclitaxel (T) may overcome the need for dual HER2-blockade with H plus pertuzumab (P). In this randomized, multicenter, phase II, open-label trial, the efficacy and safety of neoadjuvant THP vs THP-K vs TH-K are being explored (NCT03747120). Methods: 174 patients (pts) ≥18years with previously untreated, clinical stage II-III, HER2+ breast cancer will be randomized 1:1:1 to one of 3 study arms, stratified by clinical nodal status (positive vs. negative) and hormone receptor status (positive vs. negative). In arm A, pts receive THP: T at 80 mg/m2 weekly for 12 weeks, H day 1 at 8 mg/Kg (loading dose) and then 6 mg/Kg every 3 weeks x 3 doses, P day 1 at 840 mg (loading dose) and then 420 mg/Kg every 3 weeks x 3 doses (THP). In arm B, pts receive THP plus K day 1 at 200mg (flat dose) and then every 3 weeks x 3 doses (THP-K). In arm C, pts receive TH-K. Definitive surgery is 3-6 weeks after the last dose of T. After surgery, pts are treated per the treating physician’s discretion including HER2-directed therapy, endocrine therapy and radiotherapy per local clinical standards. The primary endpoint is pathologic complete response (pCR) rate in the breast and axilla (ypT0/Tis ypN0). Secondary end points include pCR rate by ypT0ypN0 and ypT0/Tis, residual cancer burden index, event free survival, breast conserving surgery rate, safety and overall survival. Exploratory correlative studies will characterize potential immune biomarkers predictive of efficacy and/or toxicity. Citation Format: Heather McArthur, Jorge Leal, David Page, Christina DiLauro Abaya, Reva Basho, Lindsey Ristow, Hannah Coleman, Stephen Shiao, Simon Knott, Monica Mita, Mourad Tighiouart, Alice Chung, Farnaz Dadmanesh, Philomena McAndrew, Scott Karlan, Sunil Verma, Armando Giuliano. Neoadjuvant HER2-targeted therapy +/- immunotherapy with pembrolizumab (neoHIP): An open label randomized phase 2 trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT2-04-04.

Abstract P1-20-29: Mastectomy rates in a single Brazilian institution through the past 15 years: Are we following the global trend?

Abstract Background: Recent medical literature reports that mastectomy rates are increasing in early breast cancer. The reasons for this have not yet been elucidated and appear to be complex and can be related to: availability of immediate reconstruction, expertise of the surgeon, increment of genetic tests and beliefs, unwillingness or impossibility of receipting radiotherapy, and information of the patients themselves. The present study aimed to demonstrate mastectomy rates throughout the years from a single Brazilian institution and to correlate it with age, neoadjuvant therapies and tumor staging. Methods: A retrospective analysis of breast cancer surgeries from patients treated at Hospital Sírio-Libanês cancer center from 2005 to 2018 was performed. The institutional database electronically of physically registered in this period included pathology, radiology, and clinical information. Chi-squared coefficient of correlation was applied for categorical variables analysis of association, and for significant findings a multivariate regression analysis was performed. All statistical analyses were performed in STATA version 15.1C. Results: Medical records from 2,942 patients treated were analyzed. 1,798 mastectomies (including nipple-sparing mastectomies and skin-sparing mastectomies) were performed against 1,144 conservative surgeries (61.11% x 38.89%). The range of mastectomy rates varied from 73.04% (2007) to 48.8% (2018) and mastectomy rates showed a slight decrease (53.84% in 2005 and 48.14% in 2018). Type of surgery (conservative, mastectomy, skin-sparing mastectomy) was associated with neoadjuvant treatment (p&amp;lt;0.001). Multiple regression analysis found that radical surgery was inversely correlated to the date of surgery, having radical strategies fewer indications along with the time (R &amp;lt; -0.001 ; t= -2.15 ; p=0.03), inversely correlated to age, being older aged patients more likely to underwent radical strategies (R= -0.004 ; t= -4.74 ; p&amp;lt;0.001), directly correlated to advanced stages (R=0.13 ; t=10 ; p&amp;lt;0.001). No significant linear correlation was found between type of surgery and neoadjuvant treatment when controlled for date, age and T staging. Conclusions: These results demonstrate that our mastectomy rates, differently from global trends, did not increase through the past 15 years. These findings are probably related to impossibility of genetic tests in this population, accurate diagnostic techniques and the achievement of higher response rates with neoadjuvant treatment. Interestingly, breast-conserving surgery rates were inversely correlated with older age, which can reflect an individualized therapeutic approach among a subgroup of patients potentially vulnerable to chemo-related toxicity. Citation Format: Thatyane EspósitoGallo Cunha, Thamyse FernandaSá Dassie, Julianne MariaSilva Lima, Max Senna Mano, Lincon Jo Mori, Samir Abdallah Hanna, Sandro ViniciusMachado Melo, Gustavo Nader Marta, Felipe EduardoMartins Andrade. Mastectomy rates in a single Brazilian institution through the past 15 years: Are we following the global trend? [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-20-29.

Abstract P5-13-03: An efficacy and safety trial of preoperative chemo-endocrine therapy in Luminal B-like (HER2-negative) breast cancer

Abstract Background: The St.Gallen consensus guideline recommends the sequential administration chemotherapy followed by endocrine therapy as postoperative therapy for the higher risk of ER-positive breast cancer patients based on results of a single study. In metastatic settings, however, several trials conducted in the 1980s' demonstrated that tumor response rates were higher when chemotherapy and tamoxifen was concomitantly administered than when chemotherapy and tamoxifen administered were given sequentially. In the preoperative settings, pathological complete response (pCR) rate can be used as a surrogate marker to predict event-free survival or overall survival in Luminal B-like (HER2-negative) breast cancer. We, therefore, designed a prospective randomized safety and efficacy trial in order to test a hypothesis that the concomitant administration of an aromatase inhibitor and chemotherapy improves pathological complete response (pCR) rate than chemotherapy alone in the preoperative setting. Trial design: This two-arm randomized clinical trial enrolled operable breast cancer patients with Luminal B-like (HER2-negative) subtype. Patients were randomly assigned (1:1) to receive preoperative chemotherapy alone or preoperative chemotherapy concurrent with endocrine therapy for 24 weeks before surgery. Chemotherapy consisted of 12 cycles of weekly paclitaxel followed by 4 cycles of every 3-week AC. Endocrine therapy consisted of anastrozole for postmenopausal patients or anastrozole plus leuprorelin for premenopausal patients. Eligibility criteria: 1)Female patients with operable and histologically confirmed invasive breast cancer; 2)HER2-negative; 3)Either ER-positive or PgR-positive; 4)Either Ki67-LI&amp;gt;=14% and NG&amp;gt;=2 or NG=3 regardless of Ki67-LI. Endpoints: Primary endpoint is the pCR rate. Secondary endpoints are the clinical response rate (RECIST), the breast-conserving surgery rate, the adverse events, and HRQOL. Results: Between March 2012 and August 2017, 70 patients were randomly assigned to chemotherapy group (n=34) or chemo-endocrine therapy group (n=36). pCR rates were 8.8 % and 2.7 % in the chemotherapy and the chemo-endocrine group, respectively (P = 0.319). Similarly, clinical complete response rates were 5.9 % and 5.6 % in the chemotherapy and the chemo-endocrine group, respectively (P = 0.745). There were no clear differences in treatment-related side effects and HRQOL between interventions. Conclusion: The concomitant administration of endocrine therapy and chemotherapy in Luminal B-like breast cancer patients is similar to chemotherapy alone in pCR rate and clinical response in the preoperative setting. Citation Format: Roichi Matsunuma, Toru Watanabe, Yasuo Hozumi, Kei Koizumi, Yasushi Ito, Hirofumi Fujita, Hiroyuki Ogura, Keigo Goto, Hiroki Mori, Noriko Sawai, Norihiko Shiiya. An efficacy and safety trial of preoperative chemo-endocrine therapy in Luminal B-like (HER2-negative) breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-13-03.

Abstract P2-09-01: Clinicopathological features and surgical management trends in individuals with breast cancer and deleterious mutations in moderate penetrance genes

Abstract Background: Moderate penetrance genes - ATM, CHEK2, and PALB2 - are often included in hereditary cancer panel testing as mutations have been linked to familial breast cancer. Limited data exists on breast cancer presentation and surgical management. We aimed to review clinicopathological features of breast cancers in patients affected by these mutations and trends in surgical management compared to unaffected cancer patients. Methods: We conducted a retrospective review of breast cancer patients, stage 0 to III, with deleterious mutations in ATM, CHEK2, and PALB2 between 2007 and 2017 at a tertiary institution. Data collected included demographics, clinicopathological tumor features, and type of treatment. These patients were compared to a control group of sporadic breast cancer patients referred for genetic counseling who tested negative for deleterious mutations via panel testing. Chi-square test, t-test, and stepwise logistic regression were used for statistical analysis. Results: A total of 145 patients had breast cancer (144 women and 1 male). There were 74 mutation-positive patients (24 ATM, 26 CHEK2, 24 PALB2) and 71 mutation-negative patients (Table 1). No differences were found in age or ethnicity among both groups. Mutation-positive patients had a higher rate of family members affected by breast cancer (79.7% vs. 52.9% in mutation-negative, p=0.0006), and tumors greater than 2 cm (63.1% vs. 42.3% in mutation-negative, p=0.0152). No differences were found on tumor histopathology, use of radiotherapy, and use of chemotherapy/endocrine therapy between the two groups. Of the patients harboring mutations, 55 patients received surgical treatment for their breast cancer after discovery of their mutation status, while the rest had surgery performed prior to genetic testing. All controls received surgery as part of treatment. Significant differences were seen in type of surgery chosen in each group. There was a lower rate of breast-conserving surgery in the mutation-positive group (25.5% vs. 46.5% in mutation-negative, p=0.0155). Additionally, 65.5% of mutation-positive patients underwent contralateral prophylactic mastectomy (CPM) compared to 33.3% in mutation-negative patients (p=0.0004). There was no association between age or ethnicity and choice of CPM. Conclusions: Mutation-positive patients are more likely to have positive family histories and larger tumors at diagnosis. They also have a higher rate of mastectomy and double the rate of CPM compared to those unaffected by mutations in moderate penetrance genes. These patients opt for more radical surgical treatment despite lack of clear guidelines for this approach. Further studies are needed to better advise physicians and patients regarding treatment decisions when encountering these mutations. Table 1. Patient, tumor, and treatment characteristicsMutationaNo mutationN=74N=71P-valueAge at diagnosis, mean (SD)48.43 (10.47)50.82 (9.84)0.1601no. (%)no. (%)EthnicityWhite49 (66.2)45 (63.4)0.8839Hispanic15 (20.3)13 (18.3)Black8 (10.8)11 (15.5)Asian2 (2.7)2 (2.8)Family history of breast cancerbYes50 (79.7)37 (52.9)0.0006No15 (20.3)33 (47.1)Stagec0 and I23 (33.8)35 (49.3)0.0644II and III45 (66.2)36 (50.7)Tumor sizec (cm)≤ 224 (36.9)41 (57.7)0.0152&amp;gt; 241 (63.1)30 (42.3)Lymph nodecPositive24 (36.4)26 (36.6)0.9752Negative42 (63.6)45 (63.4)Nuclear gradeI9 (15.8)14 (20.0)0.8284II23 (40.4)27 (38.6)III25 (43.9)29 (41.4)Estrogen receptorPositive56 (84.8)53 (74.6)0.1390Negative10 (15.2)18 (25.4)HER2/Neu receptorPositive17 (26.2)14 (19.7)0.3715Negative48 (73.8)57 (80.3)HistologyDuctal69 (93.2)63 (88.7)0.3419Lobular5 (6.8)8 (11.3)KI-67 proliferation index≤ 2017 (34.0)22 (36.7)0.7710&amp;gt; 2033 (66.0)38 (63.3)Use of chemotherapyYes47 (67.1)45 (63.4)0.6390No23 (32.9)26 (36.6)Adjuvant radiotherapyYes42 (59.2)40 (56.3)0.7340No29 (40.8)31 (43.7)Adjuvant endocrine therapyYes45 (65.2)53 (74.6)0.2235No24 (34.8)18 (25.4)Type of surgeryBCSd14 (25.5)33 (46.5)0.0155TMd41 (74.5)38 (53.5)Contralateral prophylactic mastectomy (CPM)CPM36 (65.5)23 (33.3)0.0004No CPM19 (34.5)46 (66.7)(a). ATM, CHEK2, PALB2, (b) First and second-degree relatives, (c) Tumor size, lymph node status, and stage assessed clinically, (d) Abbreviations: BCS = breast-conserving surgery, TM = total mastectomy Citation Format: Colton Pence, Jordan Berg, Natalia Partain, Navid Sadeghi, Caitlin Mauer, Sara Pirzadeh-Miller, Ang Gao, Hsiao Li, Nisha Unni, Samira Syed. Clinicopathological features and surgical management trends in individuals with breast cancer and deleterious mutations in moderate penetrance genes [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-09-01.

Abstract P6-16-03: Surgical management of DCIS during the UK Sloane audit project

Abstract Introduction The Sloane Project is a prospective cohort study, including 50% of United Kingdom screen detected ductal carcinoma in situ (DCIS) (2003-2012). We sought to examine the trends in surgical management over time for screen detected DCIS. Methods Trends in type of breast surgery were compared with DCIS radiology, pathology and breast size. Results Of 9945 patients with complete data undergoing surgical excision, 2274 (22.9%) underwent mastectomy as their first procedure, of whom 1581 (69.5%) had a simple mastectomy. Among 7877 undergoing attempted breast conserving surgery (BCS), 83 (1%) had therapeutic mammoplasty (TM). The 4:1 attempted BCS:mastectomy ratio remained consistent over time. Of attempted BCS, 882 (11.2%) were ultimately converted to mastectomy (28.9% reconstructed). Over the decade, preoperative radiological estimation of DCIS remained constant at 26mm, however pathological DCIS size steadily increased from 22.4mm (2003-4) to 25.3 (2011-12). There was no corresponding increase in mastectomy, completion mastectomy or re-excision rates. Mean tumour size excised at BCS was 19.3mm (mean), at TM was 32.4mm and at mastectomy was 39.8mm. The rates of simple mastectomy (vs reconstruction) decreased from 77.7% to 61.2% while there was a small increase in TMs (from 0.2% (2 patients) [2003-4] to 1.7% (15 patients) [2011-12]). There was a statistically (but small [8%] clinically) significant difference in mean breast volume for BCS compared to mastectomy patients (1068ml vs 988ml respectively, Student’s t-test p&amp;lt;0.0001). Mean breast volume (determined from mammography measurements) increased by 16% over the 9 years (from 1013ml to 1171ml), in parallel with increasing national BMI figures for these age groups. Conclusion Breast size and pathological size, but not radiological size of screen detected DCIS increased between 2003 and 2012, but BCS rates remained consistent. Interestingly, breast size had no apparent influence on type of surgery, although the decrease in simple mastectomy suggests breast reconstruction increased over time. Citation Format: Cliona Clare Kirwan, Sheila Stallard, Senthurun Mylvaganam, Bridget Hilton, Karen Clements, Shan Cheung, Alistair Thompson. Surgical management of DCIS during the UK Sloane audit project [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-16-03.

Long-term Results After Neoadjuvant Chemotherapy for Breast Cancer: A Single-center Experience.

We evaluated the efficacy of neoadjuvant chemotherapy (NACT) in reducing locally-advanced breast cancer (LABC) size, thus improving breast-conserving surgery (BCS) rates, as well as its long-term outcome. We analyzed 59 patients treated between 1999-2017 with NACT and subsequent surgery for LABC. We observed a tumor size reduction in 95% of cases, resulting in downstaging in 62.7%. The average tumor shrinkage was 49%. Women with a reduction in tumor size >50% after NACT had better 10-year OS rates than women with a reduction ≤50% (p=0.025). NACT allowed to perform BCS in 44% cases, whereas the remaining 56% cases underwent mastectomy. Overall, we observed recurrences in 37.2% patients. Recurrence rates after BCS and mastectomy were 30.7% (6 loco-regional and 2 distant cases) and 42.4% (5 loco-regional and 9 distant cases), respectively (p=0.07). NACT confirmed its effectiveness in reducing mastectomy rates by approximately 50%, without increasing the risk of local or distant recurrences.

Comparing Clinicopathologic Features and Surgical Treatment of Premenopausal Breast Cancer across Italy and China: Report from a Medical Exchange Program

Background: This study investigated the differences in clinicopathologic features and surgical treatment between an Italian and a Chinese cohort of premenopausal women with breast cancer, and highlighted the potential advantages of international medical exchange projects. Methods: Premenopausal women who underwent surgical treatment between 2012 and 2016 at one Italian and one Chinese institution participating in a medical exchange program were compared. Factors associated with the probability to receive mastectomy were determined via logistic analysis. Changes in surgical management at the Chinese institution in the period 2018–2019, after the exchange program, were also evaluated. Results: A total of 505 patients, 318 from Italy and 187 from China, were evaluated. The Chinese patients had more frequently advanced-stage tumours, large tumour size (30.9 vs. 18.1 mm, p < 0.01), invasive carcinoma (92.5 vs. 83.3%, p < 0.01), positive axillary lymph nodes (54.5 vs. 27.4%, p < 0.01), Her-2 positivity (36.4 vs. 22.0%, p < 0.01), and high proliferative index (55.1 vs. 30.2%, p < 0.01). Positive oestrogen receptor status and rates of triple-negative breast cancer did not differ (77.0 vs. 69.5%, p = 0.09 and 14.2 vs. 16%, p = 0.56, respectively). Mastectomy rates were higher among Chinese women (85 vs. 41%, p < 0.001), whereas use of sentinel node biopsy was more frequent among Italian women (77 vs. 33%, p < 0.001). Chinese women had more than 4-fold higher risk of receiving mastectomy. In the last 2 years, the rates of breast-conserving surgery and sentinel node biopsy at the Chinese institution increased from 15 to 23%, and from 33 to 42%, respectively. Conclusions: Tumour features and surgical strategies for premenopausal breast cancer may differ significantly between Italy and China. Since the international exchange program, patients from the Chinese institution have been offered more frequently less invasive surgery. International exchange programs can help in designing epidemiological studies which may be useful for strategies to improve breast cancer management and control.

Socioeconomic status differs between breast cancer patients treated with mastectomy and breast conservation, and affects patient-reported preoperative information

PurposeBreast cancer treatment is reported to be influenced by socioeconomic status (SES). Few reports, however, stem from national, equality-based health care systems. The aim of this study was to analyse associations between SES, rates of breast-conserving surgery (BCS), patient-reported preoperative information and perceived involvement in Sweden.MethodsAll women operated for primary breast cancer in Sweden in 2013 were included. Tumour and treatment data as well as socioeconomic data were retrieved from national registers. Postal questionnaires regarding preoperative information about breast-conserving options and perceived involvement in the decision-making process had previously been sent to all women receiving mastectomy.ResultsOf 7735 women, 4604 (59.5%) received BCS. In addition to regional differences, independent predictors of BCS were being in the middle or higher age groups, having small tumours without clinically involved nodes, being born in Europe outside Sweden, having a higher education than primary school and an intermediate or high income per household. Women with smaller, clinically node-negative tumours felt more often involved in the surgical decision and informed about breast-conserving options (both p < 0.001). In addition, women who perceived that BCS was discussed as an alternative to mastectomy were more often in a partnership (p < 0.001), not born in Sweden (p = 0.035) and had an employment (p = 0.031).ConclusionSocioeconomic factors are associated with surgical treatment even in a national health care system that is expected to offer all women the same standard of care. This should be taken into account and adapted to in preoperative counselling on surgical options in breast cancer.

Contralateral Prophylactic Mastectomy Use After Neoadjuvant Chemotherapy.

Neoadjuvant chemotherapy (NAC) for breast cancer increases breast-conserving surgery (BCS) rates, but many women opt for mastectomy with contralateral prophylactic mastectomy (CPM). Here we evaluate factors associated with CPM use in women undergoing mastectomy post-NAC. A retrospective institutional NAC database review identified women with clinical stage I-III, unilateral invasive breast cancer undergoing unilateral mastectomy (UM) or CPM mastectomy from 9/2013 to 12/2017. Clinical/pathologic characteristics, imaging, and presence of contraindications to BCS post-NAC were compared, with subset analysis of BCS candidates. The multivariable analysis was adjusted for potential confounders. Five hundred sixty-nine women underwent mastectomy after NAC, 297 (52%) UM and 272 (48%) CPM. On univariable analysis, younger age, BRCA+, lower pre-NAC clinical stage, pathologic complete response, and axillary surgery extent were associated with CPM (all p < 0.01). Favorable post-NAC clinical factors of no residual palpable disease, clinically negative nodes, complete response on breast imaging, and no post-NAC contraindication to BCS were also associated with CPM (all p < 0.01). On multivariable analysis, young age (odds ratio [OR] 0.93, 95% confidence interval [CI] 0.91-0.95), lower pre-NAC stage (OR 0.51, 95% CI 0.34-0.77), and no contraindication to BCS (OR 3.12, 95% CI 2.02-4.82) were significantly associated with CPM. Among the 203 (35%) women who had no contraindications to BCS post-NAC, 145 (71%) underwent CPM. BRCA+ and family history were reasons more frequently cited for mastectomy among CPM than UM (p < 0.001). CPM was performed in 48% of women undergoing mastectomy after NAC; younger women with earlier-stage cancers were more likely to undergo CPM. While increased use of CPM in women with more favorable disease is medically appropriate, our findings indicate a lost opportunity for use of BCS.

Non-doctoral factors influencing the surgical choice of Chinese patients with breast cancer who were eligible for breast-conserving surgery

BackgroundThe rate of breast-conserving surgery (BCS) is low in China. Many patients choose mastectomy even when informed that there is no difference in the overall survival rate compared with that of BCS plus radiotherapy. This study aimed to investigate the factors that influenced the surgical choice in patients eligible for BCS.MethodsFemale patients with breast carcinoma were enrolled in a single center from March 2016 to January 2017. They made their own decision regarding the surgical approach. Univariate analysis was employed to determine the factors associated with the different breast surgical approaches. Significant factors (defined as P < 0.05) were then incorporated into multivariate logistic regression models to determine the factors that independently influenced patients’ decision.ResultsOf the 271 patients included, 149 were eligible for BCS; 65 chose BCS and 84 chose mastectomy. On the basis of univariate analysis, patients with younger age, higher income and education, shorter admission to surgery interval, and shorter confirmed diagnosis to surgery interval were more likely to choose BCS than mastectomy (P < 0.05). Meanwhile, patients who resided in rural regions, did not have general medicare insurance, and were diagnosed with breast cancer preoperatively were more inclined to choose mastectomy than BCS (P < 0.05). The multivariate model revealed three independent influencing factors: age at diagnosis (P = 0.009), insurance status (P = 0.035), and confirmed diagnosis to surgery interval (P = 0.037). In addition, patients receiving neoadjuvant chemotherapy (NCT) were more inclined to choose mastectomy.ConclusionSurgical choice of patients eligible for BCS was affected by several factors, and age at diagnosis, confirmed diagnosis to surgery interval, and insurance status were independent factors.