Rate Of Breast-conserving Surgery Research Articles

PREDICTING RESPONSE TO NEOADJUVANT CHEMOTHERAPY IN OPERABLE BREAST CANCER: ROLE OF ER, PR, HER2 AND KI-67 INDEX

Background: Neoadjuvant (anterior or pre-operative) chemotherapy for operable breast cancer helps in down-staging of the tumor and increases the rate of breast conservation surgery. Factors that identify individuals who benet from chemotherapy have not been clearly established. This study was conducted to assess the role of estrogen receptor, progesterone receptor, HER2 and Ki-67 index in predicting response to a standard anthracycline and taxane-based chemotherapy. Methods: The study included 62 women with clinical tumor stage 1-3 and nodal stage 0 or 1. All women received preoperative anthracycline and taxane-based chemotherapy followed by surgery. Clinical and pathological response was assessed using World Health Organization (UICC) and Chevallier's criteria respectively. Results: Clinical and pathological complete response rates were 40.3% and 17.7% respectively. The pathological complete response was highest in HER2-enriched patients (45.45%) while basal-like and luminal B subtypes accounted for 27.27% each. Among those that achieved pathological complete response, 90% had Ki-67 >20, 81.8% had grade 3, 72.7% had ER negative status, 81.8% had PR negative status, 63.6% had HER2 positive status. However, there was no statistically signicant association between preoperative clinical tumor size(p=0.98), ER(p=0.053), PR(p=0.17), HER2(p=0.17), Ki-67 index(p=0.26) and pathological complete response. Conclusion: Ahigh pathological complete response was observed in tumors with high grade, high proliferative activity (high Ki-67), ER/PR negative status, HER2 over-expressing tumors and aggressive molecular subtypes such as basal-like and HER2-enriched breast cancer. However, none of these pre-chemotherapy factors showed statistically signicant association with pathological complete response.

Preoperative considerations and benefits of neoadjuvant chemotherapy: insights from a 12-year review of the Hong Kong Breast Cancer Registry.

Neoadjuvant chemotherapy (NAC) was initially used for locally advanced or inoperable breast cancers. Its extension to early disease has facilitated breast-conserving surgery (BCS). This study investigated the use of NAC in patients registered with the Hong Kong Breast Cancer Registry (HKBCR); it also assessed NAC effectiveness according to rates of pathological complete response (pCR) and BCS. Records were retrieved from the HKBCR regarding 13 435 women who had been diagnosed with invasive breast cancer during the period of 2006 to 2017, including 1084 patients who received NAC. The proportion of patients treated with NAC nearly doubled from 5.6% in 2006-2011 to 10.3% in 2012-2017. The increase was most pronounced among patients with stage II or III disease. In terms of biological subtype, substantial increases in the receipt of NAC were evident among patients with triple-negative and human epidermal growth factor receptor 2 (HER2)-positive (non-luminal) tumours. The best rates of pCR were observed in patients with HER2-positive (non-luminal) [46.0%] tumours, followed by patients with luminal B (HER2-positive) [29.4%] and triple-negative (29.3%) tumours. After NAC, the rate of BCS was 53.9% in patients with clinical stage IIA disease, compared with 38.2% in patients with pathological stage IIA disease who did not receive NAC. The use of NAC in Hong Kong increased from 2006 to 2017. The findings regarding rates of pCR and BCS indicate that NAC is an effective treatment; it should be considered in patients with stage ≥II disease, as well as patients with HER2- positive (non-luminal) or triple-negative breast cancers.

A prospective cohort study identifying radiologic and tumor related factors of importance for breast conserving surgery after neoadjuvant chemotherapy

IntroductionNeoadjuvant chemotherapy (NAC) is an established treatment option for early breast cancer, potentially downstaging the tumor and increasing the eligibility for breast-conserving surgery (BCS). The primary aim of this study was to assess the rate of BCS after NAC, and the secondary aim was to identify predictors of application of BCS after NAC. Materials and methodsThis was an observational prospective cohort study of 226 patients in the SCAN-B (Clinical Trials NCT02306096) neoadjuvant cohort during 2014–2019. Eligibility for BCS was assessed at baseline and after NAC. Uni- and multivariable logistic regression analyses were performed using covariates with clinical relevance and/or those associated with outcome (BCS versus mastectomy), including tumor subtype, by gene expression analysis. ResultsThe overall BCS rate was 52%, and this rate increased during the study period (from 37% to 52%). Pathological complete response was achieved in 69 patients (30%). Predictors for BCS were smaller tumor size on mammography, visibility on ultrasound, histological subtype other than lobular, benign axillary status, and a diagnosis of triple-negative or HER2-positive subtype, with a similar trend for gene expression subtypes. Mammographic density was negatively related to BCS in a dose-response pattern. In the multivariable logistic regression model, tumor stage at diagnosis and mammographic density showed the strongest association with BCS. ConclusionThe rate of BCS after NAC increased during the study period to 52%. With modern treatment options for NAC the potential for tumor response and BCS eligibility might further increase.

Abstract P1-09-06: Save the breast after neoadjuvant therapy – identifying radiological and tumor related factors of importance for breast conserving surgery after neoadjuvant chemotherapy

Abstract Background: Neoadjuvant chemotherapy (NAC) is an established treatment option in early breast cancer. NAC potentially downstages the tumor and, combined with oncoplastic techniques, may increase the eligibility for breast conserving surgery (BCS). NAC can also result in less surgical morbidity of the axilla if axillary clearance can be avoided. In addition, preoperative medical treatment allows for a thorough evaluation of treatment response and lays the foundation for adjuvant treatment decisions. The aim of the study was to prospectively estimate the proportion of BCS post NAC and the relation to well-defined factors associated with BCS post NAC. Materials and methods: This observational prospective cohort study included 226 patients in the SCAN-B neoadjuvant cohort (Clinical trials: NCT02306096) receiving NAC between 2014 and 2019. Eligibility for BCS was based on the assessment of the surgeon at time of diagnosis and again post NAC. All the covariables were defined at time of diagnosis from mammograms and core needle biopsies, except for pathological complete response (pCR). Treatment generally consisted of 6 to 7 three-weekly treatment cycles of anthracycline- and taxane-based chemotherapy, given in sequence. In HER2-positive disease, HER2-directed antibodies were added as appropriate.The primary aim was to estimate the proportion of BCS after NAC and the secondary aim was to evaluate factors as predictors of BCS, including gene expression and surrogate molecular subtypes (St. Gallen), breast density, and other putative modifying factors.Uni- and multivariable logistic regression analysis were performed including covariates of clinical relevance and/or associated with the outcome measures (BCS versus mastectomy). Results: The BCS rate increased during the study years, from 37% to 52%. pCR was achieved in 69 patients (30%). Predictors with a negative association to BCS were larger tumor size on mammography (T3 vs T1) (odds ratio (OR)=0.20, 95% confidence interval (CI) [0.06,0.64]), lack of visibility on ultrasound (OR=0.08, 95% CI [0.001,0.63]), lobular histological subtype vs other subtypes (OR=0,20, 95% CI [0.06,0.61)). Factors positively associated with BCS were benign axillary lymph node status (OR=2.26, 95% CI [1.26,4.06]) and surrogate molecular subtypes; patients with triple negative and HER-2 positive tumors had the highest probability of receiving BCS, 65% and 54%, respectively. Gene expression subtypes had a similar trend of being associated with BCS; patients with basal like and HER-2 enriched tumors had higher odds ratio for BCT than patients with luminal subtypes (Table 1). In the multivariable logistic regression analysis, tumor size on mammography and axillary status had the strongest association to BCS (OR=0.95, 95% CI [0.92,0.98] and OR=2.08, 95% CI [0.99,4.35], respectively). Conclusions: Our study shows that the rate of BCS after NAC increased over the study years, but mastectomy rate in the study was still close to 50%. With increasing number of patients achieving pCR after NAC, the BCS rate should be possible to increase further. Predictors of BCS after NAC were identified, and benign axillary lymph nodes and smaller tumor size defined at time of diagnosis were the strongest predictors of BCS, supporting that initial tumor stage was important for the choice of surgery after NAC. Table 1. Baseline characteristics and univariable logistic regression. 1. Determined by biopsy or sentinel node. 2. Only tumors visible on mammography. 3. Defined as ypT0/ypTis/ypN0. Citation Format: Kim Gulis, Julia Ellbrant, Pär-Ola Bendahl, Tor Svensjö, Johan Vallon-Christersson, Ida Dalene Skarping, Niklas Loman, Lisa Rydén. Save the breast after neoadjuvant therapy – identifying radiological and tumor related factors of importance for breast conserving surgery after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-09-06.

Abstract P5-09-04: Efficacy of neoadjuvant endocrine therapy compared with neoadjuvant chemotherapy in pre-menopausal patients with hormone-responsive and HER2-negative, lymph node-negative breast cancer

Abstract Background: Neoadjuvant endocrine therapy (NET) has demonstrated efficacy in post-menopausal patients with hormone-responsive and her2-negative breast cancer. This trial was designed to compare the efficacy of neoadjuvant chemotherapy (NCT) with NET in pre-menopausal patients with hormone-responsive, her2-negative and lymph node-negative breast cancer. Materials and Methods: In this prospective, randomised study, pre-menopausal patients with hormone-responsive, her2-negative and lymph node-negative breast cancer were recruited. Enrolled patients were randomly assigned (1:1) to receive either NCT or NET with goserelin and tamoxifen, followed by goserelin and anastrozole. The primary purpose was to evaluate the non-inferiority of NET compared to NCT using clinical response, assessed by ultrasound. Results: A total of 68 patients were assigned to receive NCT (n = 31) or NET (n = 37). The clinical response rate was 16.1% for NCT and 35.1% for NET (estimated difference19%, 95%CI:-1.1%-39.1%, non-inferior p = 0.002). Rates of breast-conserving surgery were similar between NCT and NET (90.3% vs 83.8%, p=0.494). Conclusions: The clinical response rate of NET is non-inferior to NCT in pre-menopausal patients with hormone-responsive, HER2-negative, lymph node-negative breast cancer. Summary of ultrasound clinical response The breast surgery and MP grading system Citation Format: chongshan gu, yingjian he, jinfeng li, tianfeng wang, zhaoqing Fan, tao ouyang. Efficacy of neoadjuvant endocrine therapy compared with neoadjuvant chemotherapy in pre-menopausal patients with hormone-responsive and HER2-negative, lymph node-negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-09-04.

Abstract OT3-25-01: Neoadjuvant HER2-targeted Therapy +/- Immunotherapy with Pembrolizumab (neoHIP): An Open Label Randomized Phase II 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, H and K administered in the curative-intent, treatment-naive setting may allow for de-escalation of cytotoxic chemotherapy; 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, multi-center trial the efficacy and safety of neoadjuvant THP vs THP-K vs TH-K are explored. Methods: 174 patients (pts) ≥18y with previously untreated, stage II-III, HER2+ breast cancer will be randomized and stratified by clinical nodal status (positive vs. negative) and hormone receptor status (positive vs. negative). In arm A, pts receive T at 80mg/m2 weekly for 12 weeks, H at 8mg/Kg (loading dose) and then 6mg/Kg every 3 weeks x 3 doses, P at 840 mg (loading dose) and then 420mg/Kg every 3 weeks x 3 doses (THP). In arm B, pts receive THP plus K at 200mg every 3 weeks x 4 doses (THP-K). In arm C, pts receive TH-K; however, in a preplanned interim analysis, arm C did not meet the pre-defined efficacy threshold and this arm was subsequently closed. Enrollment to arms A and B continue. Definitive surgery is 3-6 weeks after the last dose. After surgery, pts are treated per the treating physician’s discretion including radiotherapy per local clinical standard. Pts whose tumors are hormone-receptor positive will receive hormone therapy per local standard-of-care. The primary end point 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. Funding sources: BCRF, Merck NCT03747120 Citation Format: Heather McArthur, Jorge Henrique Santos Leal, Christina DiLauro Abaya, Sangeetha Reddy, Meredith Carter, Reva Basho, Michelle Phillips, David Chan, Hugo Hool, Dorothy Park, Mary El-Masry, Philomena McAndrew, Swati Sikaria, Laura M. Spring, Aditya Bardia, Mourad Tighiouart, Farnaz Dadmanesh, Armando Giuliano, Stephen Shiao, David B. Page. Neoadjuvant HER2-targeted Therapy +/- Immunotherapy with Pembrolizumab (neoHIP): An Open Label Randomized Phase II Trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-25-01.

Abstract P4-06-06: Neoadjuvant B27 protocol in Triple-Negative Breast Cancer: Evaluation response rate, pathological complete response rates,toxicity,and the prognosis of Adolescent and Young Adult (AYA) age group compared to older population

Abstract Background: Neoadjuvant chemotherapy (NACT) is the standard early-stage triple-negative breast cancer (TNBC) treatment. Achieving pathological complete response (pCR) is considered an essential prognostic factor with favorable long-term outcomes. Younger patients have with poorer prognosis in breast cancer. To date, few studies are comparing the prognosis of AYA and older women (≥40) with breast cancer subtypes, specifically Triple-negative breast cancer (TNBC), as AYAs had higher proportions of this subtype. Method: Retrospective review was performed on female patients who received NACT at a King Hussien Cancer Center from January 2014 to June 2020. Data were collected from patients’ electronic medical records. TNBC was histopathologically confirmed. Logistic regression analysis of predictors of pathologic complete response (pCR). Survival curves were estimated with the Kaplan-Meier method. Multivariate analysis for EFS was performed using Cox’s proportional hazards regression model, covariates included age at diagnosis (AYA vs. ≥40), tumor size, nodal status LVI and pCR Result: We analyzed 211 women with stage I-III TNBC, including 62 (29.4%) women aged 18 to 39 years (AYA) and 149 (70.6%) ≥40 years. 138 (68.3%) were node positive, and 71 (34.8%) were T3/4 disease. Median follow-up was 28.1 months, median number of ER visit during NAC is 1 (0-11), 23 (10.9 %) patients had admission during neoadjuvant chemotherapy, most commonly due to febrile neutropenia 13 (56.9%). 37 (17.5%) patients did not complete NAC, due to disease progression in 22 (10.4%), and toxicity in 15 (7.1%) patients. 195 (92.4%) patients had surgery, including 75 (35.5%) had breast-conserving surgery (BCS). 166 (76.3%) patients had objective response, and 64 (30.3%) had pCR. 170 (80.6%) received adjuvant radiotherapy, and 38 (18%) received adjuvant capecitabine. No significant differences between the AYA and the ≥40 group in terms of clinicopathological, toxicity, pCR rate, and the rate of BCS. In univariate analysis, the LVI, nodal status, pCR, and age group were significant predictors of DFS. In multivariate analysis, only PCR and age are the only independent predictor of DFS. The median DFS was worse in the AYA population 47.8 (31.21-64.39) months vs. NR in ≥40 (p-value 0.013). In patients who achieved pCR, the estimated 5-years DFS for the AYA group was 56.1% versus 86.8% for the ≥40 group, (p-value 0.71). In patients with residual disease, PFS for AYA was 34.2 (95%CI 11.5-57) months vs. 59.5 months in the ≥40 group, (p 0.009). Conclusion: Although there is no difference in pCR between the AYA age group patient treated with NACT for TNBC and the older age group, the DFS is significantly worse in the AYA than the ≥40 age group in patients with residual disease. As well, DFS is numerically worse in the AYA age vs. the ≥40 age group in patients who achieved pCR. Citation Format: Faris Tamimi, Baha’ Sharaf, Suhaib Khater, Suhaib Al-Sawajneh, Malek Horani, Khalid M. Elrabii, Anas Zayed, Hikmat Abdel-Razeq. Neoadjuvant B27 protocol in Triple-Negative Breast Cancer: Evaluation response rate, pathological complete response rates,toxicity,and the prognosis of Adolescent and Young Adult (AYA) age group compared to older population [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-06-06.

Abstract P4-06-02: Complete response of ductal carcinoma in situ to neoadjuvant systemic therapy in HER2-positive invasive breast cancer patients: a nationwide analysis

Abstract Introduction Neoadjuvant systemic therapy (NST) is increasingly applied in breast cancer to increase breast-conserving surgery (BCS) rates and to improve oncological outcomes. Ductal carcinoma in situ (DCIS) can be present adjacent to invasive breast cancer (IBC), especially in HER2-positive IBC. DCIS was previously considered to be insensitive to NST. Consequently, mastectomy rates are higher in IBC with adjacent DCIS. Recent studies have shown that DCIS can be sensitive to NST, however, only small populations were investigated. Therefore, the aim of this study was to determine the rate of complete response of adjacent DCIS in HER2-positive IBC and to assess the potential influence of clinicopathological variables in a nationwide cohort. Methods All women diagnosed with HER2-positive IBC, treated with NST and surgery between January 2010 and December 2019, were selected from the Netherlands Cancer Registry (NCR). Of these patients, all pre-NST biopsy and postoperative specimen pathology reports were obtained from PALGA, the Dutch Pathology Registry, and assessed for presence of DCIS. Response of DCIS was defined as absence of DCIS in postoperative pathology when a DCIS component was present in the pre-NST biopsy. Clinicopathological factors associated with DCIS response were assessed using logistic regression analyses. Results In total, 5834 patients were included, of whom 1443 (24.7%) had a DCIS component in the pre-NST biopsy. Mastectomy rates were higher in IBC with adjacent DCIS compared to IBC without adjacent DCIS in the pre-NST biopsy (53.6% versus 41.0%, p< 0.001). Of these 1443 patients, 743 (51.5%) showed complete response of the DCIS component. Complete response of DCIS occurred more frequently in patients who also had a complete response of IBC (63.4% versus 33.8%, p< 0.001). Multivariable logistic regression analysis showed ER negative IBC (OR 1.79; 95% CI 1.33-2.42) and treatment with HER2-targeted therapy (OR 5.97; 95% CI 1.82-19.55) to be independently associated with complete response of DCIS. Conclusion More than half of HER2-positive IBC patients with adjacent DCIS in the pre-NST biopsy showed a complete response of the DCIS component to NST. Complete response of DCIS should be considered, especially in ER-negative HER2-positive IBC and in case of complete response of IBC. Future studies should investigate the evaluation of DCIS response by imaging and the possibility of increasing breast-conserving surgery rates. Citation Format: Roxanne Ploumen, Eva Claassens, Loes Kooreman, Kristien Keymeulen, Maartje van Kats, Suzanne Gommers, Sabine Siesling, Thiemo van Nijnatten, Marjolein Smidt. Complete response of ductal carcinoma in situ to neoadjuvant systemic therapy in HER2-positive invasive breast cancer patients: a nationwide analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-06-02.

Abstract PD3-03: Preoperative robotic radiosurgery for early breast cancer: results of the phase II ROCK trial (NCT03520894)

Abstract Introduction. Breast-conserving surgery (BCS) followed by postoperative radiotherapy (RT) still represents the standard of care for early breast cancer (BC) patients. Hypofractionated schedules in maximum 15 fractions are currently accepted as the gold standard for external beam whole and partial breast irradiation (PBI). PBI for selected early BC patients allowed a shorter overall treatment duration and an improved patient compliance as compared to old-fashioned RT schedules. Preoperative PBI, due to the advantage of treating a well-defined volume, has been gaining attention in this multidisciplinary scenario. It avoids local treatment delay and might allow tumour downstaging with increased rates of BCS and improved cosmetic outcomes. Since local recurrence might be driven by biological mechanisms of radioresistance rather than geographical miss, higher dose per fraction may overcome repair mechanisms allowing tumoral cells to escape from conventional RT damage. We report the results of the phase II ROCK trial (NCT03520894), enrolling early BC patients treated with preoperative robotic radiosurgery (prRS), in terms of acute and early late toxicity, disease control, and cosmesis. Material and methods. The study recruited between August 2018 and September 2021 at the Radiation Oncology Unit of the University of Florence (Florence, Italy). Eligible patients were women aged 50+ years, with histologically proven invasive early BC, HR+/HER2- disease, without lymph vascular invasion, tumour size up to 25 mm suitable for BCS. Exclusion criteria were clinical node positive disease, multiple foci tumours, and patients with breast lesion limiting within 5 mm from the skin surface. The study aimed to prospectively assess the safety and feasibility of a single Cyberknife® (Accuray Incorporated, Sunnyvale, CA, USA) 21Gy-fraction prRS in preoperative setting, and to identify predictive factors for outcomes based on biologic and clinical features. The primary endpoint was the acute skin toxicity (from the end of prRS to surgery) according to the RTOG and the EORTC scales. Secondary endpoints were the rate of early late skin and non-skin toxicity as measured 90 days from the end of prRS, the rate of pathological complete response (pCR) according to Chevalier score. Cosmetic outcomes were prospectively scored every 6-month using the BCCT.core software. Results. From August 2018 to September 2021, a total of 70 patients were recruited and enrolled. Of those, 41 were excluded due to tumour biology exclusion criteria and 7 due to multiple foci breast disease evidenced at basal MRI. Therefore, 22 patients were successfully treated with pRS. Median age at diagnosis was 68 years (range 50-86), median tumour size was 14 mm (range 7.5-25). Required target dosimetric parameters were met in all patients, as well as normal tissue constraints. Patients received surgery after a median time of 29 days from biopsy, without any delay or postoperative complication. Overall, three G1 adverse events (13.6%) were recorded within 7 days from prRS (1 erythema, 2 breast pain). Three events (13.6%) were recorded between 7 and 30 days from prRS, one G2 breast oedema and two G1 breast pain. No acute toxicity greater than G2 was recorded. Five patients experienced early late G1 toxicity (1 breast pain, 4 breast induration). One patient reported G2 breast induration. No early late toxicity greater than G2 was observed. At a median follow up of 18 months (range 6-29.8), cosmetic results were scored excellent/good and fair in 14 and 5 patients, respectively, while 3 patients experienced a poor cosmetic outcome. Overall, pCR after surgery was reported in 2 patients (9%). Two patients received postoperative whole breast irradiation, according to histopathological results. Conclusions. ROCK trial showed that a single 21 Gy dose prRS represents a feasible technique for selected patients affected by early BC, showing a good safety profile and a promising effectiveness. Citation Format: Icro Meattini, Giulio Francolini, Vanessa Di Cataldo, Luca Visani, Carlotta Becherini, Erika Scoccimarro, Monica Mangoni, Viola Salvestrini, Laura Masi, Chiara Bellini, Raffaela Doro, Federica Di Naro, Marco Bernini, Jacopo Nori, Lorenzo Orzalesi, Simonetta Bianchi, Lorenzo Livi. Preoperative robotic radiosurgery for early breast cancer: results of the phase II ROCK trial (NCT03520894) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD3-03.

A large single-center prospective study to investigate the factors influencing the choice of breast-conserving surgery versus mastectomy in Chinese women with early breast cancer

BackgroundCompared to mastectomy, breast-conserving surgery (BCS) provides the same survival rate and a higher quality of life for patients with early breast cancer (EBC). However, Chinese women with EBC are known to have a low BCS rate. A large prospective cohort study was conducted to investigate the factors influencing the choice of BCS in this population.MethodsIn 2017, all women with unilateral EBC and eligible for BCS at our institution were enrolled. Before surgery, the patient’s trust in the surgeon and her perceived strength of the surgeon’s recommendation of BCS were measured through an in-person interview and validated ad hoc questionnaire. Multivariate logistic regressions on BCS procedure vs. mastectomy were used to estimate the odds ratio (OR).ResultsOne thousand one hundred thirty-six patients enrolled at analysis had an average age of 51.8 and tumor size of 2.4 cm. 19.9% of patients had BCS. The “strong” level of trust in the surgeon was significantly associated with BCS with an OR of 2.944 (p<0.001) when compared to the “average or under” trust. The “strong” and “moderate” strengths in surgeon recommendation for BCS were also found to be significantly associated with the BCS procedure with ORs of 12.376 (p <0.001) and 1.757 (p =0.040), respectively, compared to the “neutral or dissuaded” strength.ConclusionsStronger trust in surgeons and BCS recommendation by surgeons are associated with a higher rate of BCS in Chinese women with EBC. Interventional trials are needed to confirm this finding.

Predictors of surgery choices in women with early-stage breast cancer in China: a retrospective study

BackgroundThe breast-conserving surgery and reconstruction rate in China is relatively low when compared with those in Western countries. Moreover, predictors of surgical choices for women with breast cancer in China have not yet been explored. This study aims to explore differences in the surgical choices of women with different demographic and clinical characteristics and the predictors that influence surgical choices of women with early-stage breast cancer.MethodsThis retrospective study included women with early-stage (0-II) breast cancer who underwent surgeries at one of two Xiamen University-affiliated hospitals between 2009 and 2017. Using medical records, eleven variables were collected: the woman's age, year of diagnosis, hospital, marital status, payment method, cancer stage, presence of positive axillary lymph node, histology, neoadjuvant chemotherapy, radiotherapy, and the type(s) of surgery they chose. Binary logistic regression was used to analyse predictors of surgical choice.ResultsA total of 1,787 cases were included in this study. Of the total number of women with breast cancer, 61.3% underwent mastectomy without breast reconstruction, 26.4% underwent mastectomy with breast reconstruction, and the remaining 12.2% chose breast-conserving surgery. Women with different demographic and clinical characteristics underwent different types of surgery. Cancer stage, neoadjuvant chemotherapy, radiotherapy, and the choice of hospital were found to be predictors of breast-conserving surgery. Meanwhile, age, year of diagnosis, payment method, neoadjuvant chemotherapy, and the choice of hospital were found to be predictors of reconstruction after mastectomy in women with early-stage breast cancer.ConclusionsIn China, surgical choices for women with breast cancer have diversified. Healthcare workers should understand the surgical preferences of women of different ages. For early detection of breast cancer, knowledge of breast self-examination and breast cancer screening should be provided. Adequate information about the safety of reconstruction and advocacy for medical insurance coverage of reconstruction should be offer. Breast surgeons need specialised training and standardising protocols towards different types of breast surgery. These actions will help women make better, well-informed decisions about their breast surgeries.

Mixed invasive ductal lobular carcinoma is clinically and pathologically more similar to invasive lobular than ductal carcinoma.

Mixed invasive ductal lobular carcinoma (mDLC) remains a poorly understood subtype of breast cancer composed of coexisting ductal and lobular components. We sought to describe clinicopathologic characteristics and determine whether mDLC is clinically more similar to invasive ductal carcinoma (IDC) or invasive lobular carcinoma (ILC), using data from patients seen at the University of Pittsburgh Medical Center. We observed a higher concordance in clinicopathologic characteristics between mDLC and ILC, compared to IDC. There is a trend for higher rates of successful breast-conserving surgery after neoadjuvant chemotherapy in patients with mDLC compared to patients with ILC, in which it is known to be lower than in those with IDC. Metastatic patterns of mDLC demonstrate a propensity to develop in sites characteristic of both IDC and ILC. A meta-analysis evaluating mDLC showed shared features with both ILC and IDC with significantly more ER-positive and fewer high grades in mDLC compared to IDC, although mDLCs were significantly smaller and included fewer late-stage tumours compared to ILC. These findings support clinicopathologic characteristics of mDLC driven by individual ductal vs lobular components and given the dominance of lobular pathology, mDLC features are often more similar to ILC than IDC. This study exemplifies the complexity of mixed disease.

1LBA - Complete response of ductal carcinoma in situ to neoadjuvant systemic therapy in HER2-positive invasive breast cancer patients: a nationwide analysis

Background: Neoadjuvant systemic therapy (NST) is increasingly applied in breast cancer to increase breast-conserving surgery (BCS) rates and to improve oncological outcomes. Ductal carcinoma in situ (DCIS) can be present adjacent to invasive breast cancer (IBC), especially in HER2-positive IBC. DCIS was previously considered to be insensitive to NST. Consequently, mastectomy rates are higher in IBC with adjacent DCIS. Recent studies have shown that DCIS can be sensitive to NST, however, only small populations were investigated.

The State of Breast Cancer Reconstruction in Virginia: An Evidence-Based Framework for Identifying Locoregional Health Disparities.

Age, race, socioeconomic status, and proximity to plastic surgeons have been shown to impact receipt of reconstruction after mastectomy in several national studies. Given that targeted outreach efforts and programs to address these discrepancies would occur locoregionally, investigation of these reconstructive trends on a state level is warranted. Patients diagnosed with breast cancer in Virginia between 2000 and 2018 were identified in the Virginia Department of Health Cancer Registry. Patients who underwent mastectomy breast conservation surgery, and/or breast reconstruction at the time of oncologic surgery were identified. Patient demographics were analyzed, and logistic regression analyses were used to determine the likelihood of receipt of mastectomy, receipt of mastectomy versus breast conservation surgery, receipt of mastectomy with reconstruction versus mastectomy alone, and receipt of mastectomy with reconstruction versus breast conservation surgery with respect to the demographic variables. Geographically weighted regression analyses were also performed to determine impact of geographic location on receipt of mastectomy and reconstruction after mastectomy. A total of 78,682 patients in Virginia underwent surgical treatment for breast cancer between 2000 and 2018. Living outside a metropolitan area, increased age, lower socioeconomic status, non-White race, and lower number of plastic surgeons within 50 miles were associated with decreased rates of postmastectomy reconstruction. Rural setting, lower socioeconomic status, and lower plastic surgeon supply were also associated with decreased rates of breast conservation surgery. Reconstruction after mastectomy was lowest in the northwest, central, and southwest regions of Virginia. Within the state of Virginia, programs to improve access to breast reconstruction for patients residing in rural regions, as well as non-White patients, older patients, and those in lower socioeconomic groups should be implemented. Future studies would implement and study the efficacy of such outreach programs, which could then be applied and tailored to other states or regions to address sociodemographic disparities in access to breast reconstruction.

Assessment of Quality of Life in Patients of Mastectomy With Chemotherapy.

Background: Breast cancer is one of the most common cancers in India as well as the world. In India, 48% of patients with breast cancer are below 50 years of age, indicating a huge age shift in the last 25 years. Breast cancer in an early age group increased the five-year survival rate and increased life expectancy has created a large group of breast cancer survivors who battle scars of disease as well as treatment. Standardized multimodal treatment is either not affordable or not available, so the breast conservation surgery rate is very low. Mastectomy is still the most common modality of treatment, particularly in rural areas. In addition to psychological, social, economic, and family barriers to obtaining the diagnosis and treatment needed, economic barriers like the cost of travel and lost wages are important factors influencing the choice of treatment. Mastectomy represents a deep burden for women with breast cancer. Very little is known about the psychological consequences over time and the quality of life (QOL) of women so treated, with or without breast reconstruction. Conflicting literature is available regarding QOL after mastectomy. The survival rates of breast cancer are increasing. They are reported in the range of 80-90% in western countries while in the range of 60% in the Indian scenario. With high survival rates in cancer, the focus needs to shift from mortality indicators to QOL indicators. The QOL that these survivors experience is a comparatively newer domain of study. Though there are many instruments for assessment of breast QOL of breast cancer patients with numerous studies in western literature, QOL studies in Indian rural population are far less, and urban studies cannot be extrapolated because the method of treatment differs, with breast conservation being more common in urban population. Hence, the present study is undertaken to assess the QOL in patients who have undergone mastectomy and ongoing chemotherapy or completed chemotherapy recently using a relatively newer instrument, i.e., the Quality of Life Instrument - Breast Cancer Patient version.Methodology: The present study was a cross-sectional study conducted at a rural tertiary healthcare center on mastectomy patients attending the outpatient department and admitted to the hospital. All the female patients of carcinoma breast treated with a mastectomy who were receiving the adjuvant or neoadjuvant chemotherapy or were within one year of completion of chemotherapy irrespective of age at diagnosis were included in this study. The assessment was performed by interview method using a questionnaire.Results: In this study, 44.90% of the patients were <50 years old and 55.10% were more than 50 years old. Among them, 28.57% were illiterate while only 20.41% had graduate education. The majority (61.22%) were from the low socioeconomic class. Majority of women presented in the late stages of the disease, with 61.22% presenting in the third stage and only three (6.12%) presenting in the first stage of the disease. The overall global QOL score was 49 ± 2.6 and fear was assessed. Patients scored better in the physical, psychological, social, and spiritual domains, with an average score of more than 50. The worst scores were observed among distress of illness or treatment.Conclusions: The present study shows that the average QOL scores in rural Indian women after mastectomy are moderate. Global scores and other indicators show moderate QOL.

Breast Conservative Surgery for Breast Cancer: Indian Surgeon’s Preferences and Factors Influencing Them

BackgroundIt is well established that disease-free survival and overall survival after breast conservation surgery (BCS) followed by radiotherapy are equivalent to that after mastectomy. However, in Asian countries, the rate of BCS continues to remain low. The cause may be multifactorial including the patient’s choice, availability and accessibility of infrastructure, and surgeon’s choice. We aimed to elucidate the Indian surgeons’ perspective while choosing between BCS and mastectomy, in women oncologically eligible for BCS.MethodsWe conducted a survey-based cross-sectional study in January–February 2021. Indian surgeons with general surgical or specialised oncosurgical training, who consented to participate were included in the study. Multinomial logistic regression was performed to assess the effect of study variables on offering mastectomy or BCS.ResultsA total of 347 responses were included. The mean age of the participants was 43 ± 11 years. Sixty-three of the surgeons were in the 25–44 years age group with the majority (80%) being males. 66.4% of surgeons ‘almost always’ offered BCS to oncologically eligible patients. Surgeons who had undergone specialised training in oncosurgery or breast conservation surgery were 35 times more likely to offer BCS (p < 0.01). Surgeons working in hospitals with in-house radiation oncology facilities were 9 times more likely to offer BCS (p < 0.05). Surgeons’ years of practice, age, sex and hospital setting did not influence the surgery offered.ConclusionTwo-thirds of Indian surgeons preferred BCS over mastectomy. Lack of radiotherapy facilities and specialised surgical training were deterrents to offering BCS to eligible women.

Pegylated Liposomal Doxorubicin, Docetaxel, and Trastuzumab as Neoadjuvant Treatment for HER2-Positive Breast Cancer Patients: A Phase II and Biomarker Study.

BackgroundCombined neoadjuvant chemotherapy with trastuzumab and pertuzumab is the standard regimen for human epidermal growth receptor 2 (HER2)-positive breast cancer (BC). However, pertuzumab is not available because it is not on the market or covered by medicare in some regions or poor economy. Anthracyclines and taxanes are cornerstones in BC chemotherapy, and their combination contributes to satisfactory efficiency in neoadjuvant settings. Nonetheless, concomitant administration of trastuzumab and an anthracycline is generally avoided clinically due to cardiotoxicity. Pegylated liposomal doxorubicin (PLD) is less cardiotoxic compared with traditional anthracyclines. Here, we conducted this prospective study to evaluate the efficacy, safety, and potential biomarkers for PLD plus trastuzumab and docetaxel as neoadjuvant treatment in HER2-positive BC.Patients and MethodsPatients with stage II or III HER2-positive BC were recruited in this multicenter, open-label, single-arm, phase II study. Eligible patients were given 6 cycles of PLD plus docetaxel and trastuzumab. Primary endpoint was total pathological complete response (tpCR, ypT0/is ypN0). Secondary endpoints were breast pathological complete response (bpCR, ypT0/is), objective response rate (ORR), operation rate, breast-conserving surgery rate, and safety. Metadherin (MTDH), glutaminyl-peptide cyclotransferase (QPCT), topoisomerase II alpha (TOP2A), programmed death ligand 1 (PD-L1), and tumor-infiltrating lymphocytes (TILs) were evaluated in BC tissues pre-neoadjuvant for potential biomarkers.ResultsBetween March 2019 and February 2021, 54 patients were enrolled, 50 were included in the analysis, and 35 (70.0%) completed 6 cycles of neoadjuvant treatment. Forty-nine (98.0%) patients underwent surgery with a breast-conserving rate of 44.0%. The tpCR rate, bpCR rate, and ORR were 48.0% (95% CI, 33.7%–62.6%), 60.0% (95% CI, 45.2%–73.6%), and 84.0% (95% CI, 70.9%–92.8%), respectively. tpCR was associated with MTDH (p = 0.002) and QPCT (p = 0.036) expression but not with TOP2A (p = 0.75), PD-L1 (p = 0.155), or TILs (p = 0.76). Patients with HR-negative status were more likely to achieve bpCR compared with those with HR-positive status (76.2% vs. 48.3%, p = 0.047). Grade ≥3 adverse events occurred in 38.0% of patients. Left ventricular ejection fraction decline by ≥10% was reported in 18.0% of patients, and no patient experienced congestive heart failure.ConclusionsPLD plus docetaxel and trastuzumab might be a potential neoadjuvant regimen for HER2-positive BC with a high tpCR rate and manageable tolerability. MTDH and QPCT are potential predictive markers for tpCR.

Abstract 749: SimBioSys TumorScope accurately models and predicts response to neoadjuvant therapy in breast cancer - Validation study

Abstract Neoadjuvant Therapy (NAT) for breast cancer results in higher rates of breast conservation surgery. Importantly, there is data supporting the use of multiple NAT regimens, with little guidance as to which one would be most effective for a given patient. Thus, tools that can accurately predict patient outcome before cancer treatment can provide guidance during treatment planning and increase the chances of therapy success. Here we present the first biophysical modelling platform, TumorScope (TS), capable of constructing a 3D model of the tumor microenvironment by integrating models for tumor morphology, metabolism, drug delivery and behavior, and vascularity. Thereby allowing visualization of response to multiple NATs for a given tumor. TS integrates patient data to create an in-silico tumor model capturing the tumor response trajectory, volume, dimensions, pathological complete response (pCR), residual cancer burden and tumor morphology, and risk of recurrence (ROR). To illustrate the clinical applicability and to validate TS we performed a single center validation study. Previously acquired pre-treatment standard of care (SOC) diagnostic data (demographics, drug regimen, imaging (DCE MRI), and pathology) was used as TS inputs. Using this baseline data only, TS predicted weekly volumetric response through the treatment time and used simulated residual volume to predict pCR and assessed the ROR. The validation was performed using ground truth from post treatment assessment of pCR, radiographic volumes extracted from MRIs and ROR information. A chart review was performed to identify consecutive patients who had received NAT and had a corresponding pre-treatment MRI at University of Cincinnati. A validation set was generated from this list and data processed through TS (n=81, after excluding 9 patients with poor quality DCE-MRIs). TS predicted pCR was predefined as a residual tumor volume &amp;lt; 0.01 cm3 or a 99.9% or greater reduction in tumor volume. Performance metrics of TS were calculated. TS response (pCR vs. residual) prediction accuracy had an area under the curve (AUC) =0.912 with sensitivity and specificity of 88.9% and 92.5%, respectively. The performance was robust across all subtypes. Using SOC diagnostic data TS predicted the reduction in tumor volume with a median absolute volumetric error of 3.4% vs radiographic volume from pre-surgery DCE MRIs (n=59). TS prognostic ROR (High vs Low) had a hazard ratio [HR] 12.705, p=0.01 which was comparable as a prognostic indicator to actual pCR which had a [HR] 5.81, p=0.08. In summary, TS accurately predicts patient-specific response to NAT in early breast cancer using only baseline SOC pre-treatment data. This approach to a comprehensive view of the tumor represents a major step-forward in personalized clinical decision making. The results from this study will be used in a multi-center meta-analysis of TS performance characteristics. Citation Format: Gregory H. Norris, John Pfeiffer, Yuhan Zhang, Hope R. Esslinger, The SimBioSys Team, Vinita Takiar. SimBioSys TumorScope accurately models and predicts response to neoadjuvant therapy in breast cancer - Validation study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 749.

Neoadjuvant HER2-targeted therapy +/- immunotherapy with pembrolizumab (neoHIP): An open-label randomized phase II trial.

TPS624 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, H and K administered in the curative-intent, treatment-naive setting may allow for de-escalation of cytotoxics; 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 explored. Methods: 174 patients (pts) ≥18y with previously untreated, stage II-III, HER2+ breast cancer will be randomized and stratified by clinical nodal status (positive vs. negative) and hormone receptor status (positive vs. negative). In arm A, pts receive T at 80mg/m2 weekly for 12 weeks, H at 8mg/Kg (loading dose) and then 6mg/Kg every 3 weeks x 3 doses, P at 840 mg (loading dose) and then 420mg/Kg every 3 weeks x 3 doses (THP). In arm B, pts receive THP plus K at 200mg every 3 weeks x 4 doses (THP-K). In arm C, pts receive TH-K. Definitive surgery is 3-6 weeks after the last dose. After surgery, pts are treated per the treating physician’s discretion including radiotherapy per local clinical standard. Pts whose tumors are hormone-receptor positive will receive hormone therapy per local standard-of-care. The primary end point 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. Clinical trial information: NCT03747120.

Preliminary outcomes for non-metastatic breast cancer before and during the coronavirus disease 2019 pandemic at community cancer centers.

e18634 Background: The Coronavirus Disease 2019 (COVID-19) pandemic has changed the delivery of cancer care and may have impacted the treatment outcomes. This study described the preliminary outcomes in non-metastatic breast cancer (BC) patients before and during the COVID-19 pandemic. Methods: This retrospective study included adult patients newly diagnosed with non-metastatic BC at two community cancer centers in southeast Texas. Patients diagnosed from 1/2018-10/2018 were included in the control group. Patients diagnosed from 4/2020-1/2021 were included in the COVID-19 group. The key outcomes were progression free survival (PFS), overall survival (OS), breast conserving surgery (BCS) rate, pathological complete response (PCR) rate, and time to treatment initiation (TTI). Results: The study included 74 patients (Table). The proportion of patients with self-detected BC was numerically higher in the COVID-19 group (55%) compared to the control group (36%), although this was not statistically significant (P = 0.09). The median follow-up periods were 38 (IQR: 36-43) months in the control group and 15 (IQR: 13-17) months in the COVID-19 group. No significant difference was observed in PFS (P = 0.74), with 1-year PFS of 93% (95%CI: 80%-98%) in the control group and 100% in the COVID-19 group. No significant difference was observed in OS (p = 0.22), with 1-year OS of 98% (95%CI 85%-100%) in the control group and 100% in the COVID-19 group. No significant difference was observed in TTI between control (51 days) and COVID-19 groups (52 days) (95%CI: -14 to 13; P = 0.91). Among patients who received neoadjuvant systemic therapy and surgery, BCS rates were 29% (5/17) in the control group and 50% (5/10) in the COVID-19 group (P = 0.42). Among patients who had triple negative or HER2 positive BC and received neoadjuvant systemic therapy and surgery, PCR rates were 57% (4/7) in the control group and 33% (1/3) in the COVID-19 group. Conclusions: Although total patient volume decreased during the COVID-19 pandemic, no significant difference was observed in clinical outcomes when comparing patients diagnosed with non-metastatic BC during and prior to the pandemic. Ongoing monitoring with a larger study population and longer follow-up period will help to elucidate the long-term impact of COVID-19 on BC treatment.[Table: see text]