Evaluation of Recurrence Rate in Canadian Patients With Stage II/III HR+/HER2− Early Breast Cancer in the Real-World Setting

e23303 Background: Breast cancer is the most prevalent cancer and second leading cause of cancer-related mortality among Canadian women. Most of cases belong to the HR+/HER2- subtype, representing approximately two-thirds of all instances. Treatment for this subtype encompasses a multifaceted approach with a curative intent. This real-world evidence study aims to comprehensively analyze the clinical outcomes of Canadian patients diagnosed with early-stage HR+/HER2- breast cancer, focusing on recurrence rates after initiation of adjuvant endocrine therapy to identify opportunities for enhancing patient care. Methods: This is a retrospective, longitudinal cohort study involving 541 patients enrolled in the pan-Canadian cancer patient registry PMT (Personalize My Treatment), with newly diagnosed or recurrent stage II or III HR+/HER2- breast cancer between January 1st, 1996, and May 31st, 2022. We evaluated disease recurrence rates, time to recurrence, and overall survival (OS). Furthermore, the study explored duration of endocrine therapy (ET) in the adjuvant setting. Results: 409 patients received adjuvant ET representing 75.6% of the total cohort, emphasizing the role of ET as standard of care for adjuvant treatment in this patient population. The median duration of adjuvant ET was 4.5 years. In the overall adjuvant patient population, recurrence rates progressively increased over time from 13.2% after 2 years, 21.4% after 3 years, 30.3% after 5 years, and peaking at 58.4% after 10 years. Median time to recurrence for the overall patient population on ET was 7.76 years. OS rate for patients on ET was 94.6% at 5 years and 78.3% at 10 years. Conclusions: This study marks a pioneering real-world analysis utilizing pan-Canadian EHR data, demonstrating increasing recurrence rates over time in HR+/HER2- early breast cancer. It highlights the high unmet need in stage II and stage III breast cancer, with 1 patient out of 3 recurring after 5 years, and more than half recurring after 10 years despites adjuvant treatment with ET alone. This indicates the need for more efficacious and tolerable treatment options to reduce short- and long-term recurrence and to prolong survival, not only in the higher risk patient population, but in the overall HR+/HER2- breast cancer patients at increased risk of recurrence.

Background: Hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) is the most prevalent breast cancer (BC) subtype(≈60% of all BC in Spain), 95% of which are diagnosed in early stage. Despite several treatment options, approximately 20%-25% of them will experience metastatic relapse. Early and accurate identification of patients at high risk of recurrence is critical to improve patient outcomes. It would be relevant to know how high risk patients are identified and managed in Spain. The primary objective was to describe the current approaches to patient management and standards of care for patients with early stage (I-IIIc) HR+/HER2- BC in a real world setting in Spain.Methods: Real-world data were drawn from the Adelphi Early BC I Disease Specific Program. Data included physicians´ (medical oncologists) subjective perceptions such as factors used to determine patient´s risks of recurrence, and objective variables relating to the next 8 consecutive patients with HR+ HER2- BC they consulted and completed patient record forms for, such as demographic, clinical and gene expression profiles. Data were collected between June and October 2019. The sample was analyzed to identify patients similar to those meeting the high risk of recurrence criteria used in the monarchE (mE) trial: ≥4 positive nodes, OR 1-3 positive nodes AND [grade 3 or tumor ≥5 cm or Ki-67 ≥20%]. Those not meeting the criteria were categorised as Low/moderate (L/M) risk. Results: 50 oncologists provided data on 400 consecutive patients, of which 81 (20%) were categorized as high risk. Patients´ mean age was 58 years old at diagnosis and initiated first adjuvant treatment (AT) within four months of diagnosis. 19% had family history of BC, their disease stage was predominantly II (50%), 57% had grade 2 tumors and 74% had a tumor size of 1-3cm. 50 patients (13%) met high risk clinical pathologic criteria (≥4 positive nodes, OR 1-3 positive nodes AND [grade 3 or tumor ≥5 cm]) and an additional 31 patients (8%) met high risk mE criteria based on having a Ki-67 expression of ≥20%.At diagnosis, high risk patients compared to L/M tended to be younger (mean 54,3 vs 58,5 years), with higher likelihood of BC family history (32% vs 16%), more advanced disease at diagnosis (99% vs 59% stage II or III), more likely to have grade 3 tumors (41% vs 14%) and tumors >3cm (32% vs 14%). The most common biomarker/genetic tests at diagnosis were ER, PgR and Ki67, used in over 95% of patients.Genomic assays of the tumors were performed in 35% of patients, of which the most common were Oncotype Dx (58%) and MammaPrint (22%). High risk patients were less likely to have genomic assays (15% vs 40% received any). Genomic assays were more often conducted prior to starting AT therapy (66%) than at initial diagnosis (38%).Neoadjuvant and first adjuvant treatments are described in table 1. Factors frequently considered by oncologists (>45% of respondents) to evaluate risk of recurrence were tumor stage, size and grade, nodal, HER2 and HR status, genomic assays and Ki-67 expression level. Conclusion: One in five patients were classified as high risk according to mE criteria, although oncologists considered additional factors to categorize patients as high risk level in their daily practice. Consequently, many patients of L/M risk according to mE criteria could still be considered as high risk by their physicians, as suggested by nearly half of patients receiving ChT treatment as adjuvant therapy. Proportion of patients that were prescribed each class in each setting (not mutually exclusive)ChemotherapyAnthracyclineTaxaneEndocrine therapyAromatase inhibitorTamoxifenTargeted therapyTotal sampleNeoadjuvant therapy n (%)n (%)n (%)n (%)n (%)n (%)n (%)n (%)Overall (n=400)75 (19)69 (92)60 (80)64 (85)28 (37)22 (29)6 (8)-High risk (n=81)17 (21)16 (94)15 (88)16 (94)8 (47)7 (41)1 (6)-L/M risk (n=319)58 (18)53 (91)45 (78)48 (83)20 (34)15 (26)5 (9)-Total sampleFirst adjuvant n (%)n (%)n (%)n (%)n (%)n (%)n (%)n (%)Overall (n=400)400 (100)217 (54)129 (32)132 (33)256 (64)177 (44)79 (20)1 (0)High risk (n=81)81 (100)66 (81)56 (69)50 (62)27 (33)18 (22)9 (11)1 (1)L/M risk (n=319)319 (100)151 (47)73 (23)82 (26)229 (72)159 (50)70 (22)- Citation Format: Miguel Martín, Jose Ángel García Sáenz, Isabel Blancas, Alberto Molero, Manuel Atienza, Jose Manuel Cervera, Jacqueline Brown, Alex Rider, Rhys Williams, Emilio Alba. Patient profiles, management and treatment patterns in HR+, HER2- early breast cancer in a real-world setting in Spain [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-10.

P3-12-15: Clinical characteristics, treatment patterns, and survival outcomes in women with early triple-negative (TN) or hormone receptor-positive/human epidermal growth factor receptor-2 negative (HR+/HER2−) breast cancer (BC) in the real-world (RW) setting

Background: As the treatment landscape of human epidermal growth factor receptor 2-negative (HER2–) early breast cancer (BC) evolves, an understanding of treatments given in real-world settings to elderly patients with HER2– early BC is needed to gain insight into the potential unmet needs of this population for whom clinical data are limited. This study described demographics, clinical characteristics, and neoadjuvant and adjuvant treatment patterns in elderly patients with HER2– early BC in the United States. Methods: This retrospective study used SEER-Medicare data (2010–2019) to identify patients aged ≥66 years with HER2– early (Stage I–III) BC receiving primary surgery. Patient characteristics were evaluated at primary surgery or at BC diagnosis. Neoadjuvant and adjuvant therapies were defined as any National Comprehensive Cancer Network-recommended regimens received between BC diagnosis and primary surgery, and during the 180-day period following primary surgery, respectively. Patient characteristics were described using means and standard deviations (SDs) for continuous characteristics, and frequencies and proportions for categorical characteristics. Neoadjuvant and adjuvant therapies were summarized using frequencies and proportions. All analyses were conducted for the overall population and stratified by breast cancer subtype (hormone receptor-positive [HR+]/HER2– vs. triple negative BC [TNBC]) and stage at diagnosis (Stage I vs. Stage II/III). Results: Of 28,655 eligible patients, 25,899 (90.4%) had HR+/HER2– BC and 2,756 (9.6%) had TNBC; 17,961 (62.7%) had Stage I BC and 10,694 (37.3%) had Stage II/III BC. Mean (SD) age at diagnosis was 75.8 (6.4) years, mean (SD) National Cancer Institute comorbidity index was 1.9 (2.1), and 23.7% received single or multi-gene testing for a breast cancer gene 1 and/or 2 (BRCA1/2) mutation (HR+/HER2– BC: 24.6%; TNBC: 15.5%), with most (86.3%) testing occurring after primary surgery. Relative to HR+/HER2– BC patients, TNBC patients were less likely to present with Stage I disease (46.7% vs. 64.4%), had a larger mean tumor size at diagnosis (2.6 cm vs. 1.9 cm), and higher-grade tumors (Grade III or IV: 70.6% vs. 14.6%). TNBC patients were also more likely to receive neoadjuvant chemotherapy (90.9% vs. 35.3%) and adjuvant radiation therapy (81.2% vs. 66.4%) than HR+/HER2– BC patients (Table 1). By BC stage, neoadjuvant therapy was more common among Stage II/III patients relative to Stage I patients (12.3% vs. 2.7%), with most (90.4%) neoadjuvant chemotherapy use observed among Stage II/III patients. Adjuvant therapy use was similar between Stage I and Stage II/III patients (87.4% vs. 88.1%) and the most common adjuvant therapies across both subgroups were endocrine therapy (85.2% vs. 82.2%) and radiation therapy (68.5% vs. 66.1%). Conclusion: In elderly patients with HER2– early BC, treatment with adjuvant therapy was common, while neoadjuvant therapy was limited. Moreover, one in four HER2– early BC patients were tested for a BRCA1/2 mutation in real-world clinical practice. Our findings highlight the need for a better understanding of the role of increased and timely BRCA1/2 testing to inform optimal treatment strategies across neoadjuvant and adjuvant settings in this population. Table 1. Treatment Patterns Among Patients with TNBC and HR+/HER2– Early Breast Cancer Citation Format: Jagadeswara Earla, Allison Kurian, Kalé Kponee-Shovein, Ambika Satija, Yan Song, Nathaniel Downes, Malena Mahendran, Qi Hua, Arun Kumar, Jaime Mejia. Real-World Treatment Patterns in Elderly Patients with HER2-Negative Early Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-16-08.

Adjuvant bisphosphonates in patients with breast cancer: does the potency matter?

Does adjuvant therapy reduce postmetastatic survival?

Background: Hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer (BC) accounts for ∼70% of early-stage cases. A systematic literature review was conducted to summarize the perioperative (neoadjuvant therapy and/or adjuvant therapy) treatment regimens and the efficacy outcomes in this setting. Methods: Embase, Medline and Cochrane were searched from database inception to May 19th 2023; relevant conferences were also searched from 2021 to 2023 (inclusive). English language publications of randomized control trials (RCTs) including adult patients with early-stage HR+/HER2- BC receiving neoadjuvant therapy and/or adjuvant therapy (excluding endocrine [ET] only neoadjuvant therapy) were included. Results: Of 3,490 records identified, 71 RCTs (window of opportunity: n=2 [3%], Phase II: n=39 [55%], Phase III: n=27 [38%], not reported: n=3 [4%]) were included. The cumulative sample size was 78,457, which ranged from 21 to 9,719 across the trials. The HR status among the included populations of these trials were reported as follows: HER2-/HR+ (n=57 trials) and HER2-/ER+ (n=14). Mean/median age of the patients varied from 46.9 to 65.6/46 to 76 years, respectively across the 26 trials where age was reported. Anatomical stage varied across studies (Stage I [Range]: 0.1% to 59%, Stage II: 25.3% to 100%, Stage III: 5% to 74.1%). Among studies which reported histological grade, the proportion of patients with grade 3 disease ranged from 3% to 55%. Where reported, nodal status varied among patient cohorts (N0: 5.1% to 98.1%, N1: 33.1% to 67.4%, N2: 2% to 37.0%, N3: 1.6% to 13.6%). Treatment interventions varied across the RCTs. Chemotherapy (CT) with or without ET was included in 33 studies overall; as neoadjuvant treatment in 21 RCTs (30%), adjuvant treatment in 9 RCTs (13%) and both neoadjuvant and adjuvant in 3 RCTs (4%). Targeted therapies (including CDK4/6, PARP, PI3K and AKT inhibitors) with or without CT or ET was included as neoadjuvant treatment in 19 RCTs (27%) and as adjuvant treatment in 6 RCTs (8%). Immunotherapies with or without CT or targeted therapies were included as neoadjuvant treatment in 12 RCTs (17%). Antibody drug conjugates (SGN-LIV1A) were included in 1 RCT (1%). Primary endpoints included pathologic complete response (pCR: n=32; 45%), invasive disease-free survival (IDFS: n=8; 11%), disease free survival (DFS: n=5; 7%), objective response rates (ORR: n=5; 7%) and change in Ki67 expression (n=3; 4%). Event free survival (EFS) was not reported as a primary endpoint in any included trials. Median duration of follow-up ranged between 0.5 to 14.4 years across the included trials. Conclusions: Heterogeneity was observed in terms of patient characteristics, treatment regimens, and outcome measures among clinical trials in perioperative setting. EFS, a relevant efficacy outcome measure for perioperative interventions, was not reported as a primary endpoint in the existing literature; to date clinical trials evaluating perioperative neoadjuvant plus adjuvant regimens in HR+/HER2- BC have been limited. An emerging trend for clinical trials investigating immunotherapy-based perioperative neoadjuvant plus adjuvant interventions was observed, reflective of the unmet need for innovative therapies among patients with early-stage high-risk HR+/HER2- BC. Citation Format: Peter Schmid, Jagadeswara Rao Earla, Astha Jain, Duygu Bozkaya, Rahul Kamath, Kim M Hirschfield, Prabhakar Pandey, Amin Haiderali. Perioperative treatment regimens and efficacy outcome measures in early-stage HR+/HER2- breast cancer: A systematic literature review of randomized controlled trials [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-09-28.

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

CDK4/6 inhibitors as neoadjuvant treatment in breast cancer—what can we learn?

Background: mTNBC represents an area of high unmet need, yet studies assessing real-world outcomes in pts treated in 2L are limited. We describe treatment patterns and outcomes in mTNBC pts receiving 2L treatment primarily in community cancer care clinics in the USA. Methods: Pts aged ≥18 y with a confirmed diagnosis of mTNBC between 1 Jan 2011 and 28 Feb 2017 and who received 2L therapy were identified from the Flatiron Health electronic health record-derived database. Overall survival (OS) and time to next treatment (TTNT) were assessed as primary outcomes using Kaplan–Meier methods in both the overall population and subgroups of pts receiving the most commonly used agents (capecitabine, taxane, gemcitabine). Results: Most of the 623 pts analyzed were White (62.9%) and received care in community clinics (94.9%). The most commonly used previous first-line (1L) regimens in this 2L pt population were: capecitabine (14.0%), cyclophosphamide/doxorubicin (11.6%), carboplatin/gemcitabine (9.3%), paclitaxel (7.1%), and nab-paclitaxel (7.1%); the remaining 51.0% of pts received 95 different 1L regimens. The most common 2L treatments were monotherapy regimens: capecitabine (10.9%), paclitaxel (9.3%), eribulin (9.0%), nab-paclitaxel (8.2%), and gemcitabine (7.7%); the remaining 54.9% of pts received 120 different 2L regimens. Selected demographic, clinical, and treatment characteristics and outcomes after median follow-up of 8.5 (interquartile range [IQR] 4.5–15.7) mo are shown below. No. of pts (%)All pts (n=623)Selected subgroups by agent-containing regimen* Capecitabine (n=101)Taxane (n=222)Gemcitabine (n=111)Median age at initial metastatic diagnosis, y (IQR)58 (50–68)60 (53–67)58 (50–68)61 (51–70)Recurrent458 (73.5)81 (80.2)130 (58.6)93 (83.8)TFI >12 mo†104 (47.1)18 (43.9)21 (42.9)23 (57.5)TFI ≤12 mo†117 (52.9)23 (56.1)28 (57.1)17 (42.5)TFI missing237408153De novo164 (26.3)20 (19.8)92 (41.4)18 (16.2)Missing1 (0.2)000Median time from 1L to start of 2L, mo (IQR)3.7 (2.1–6.4)4.2 (2.6–7.5)2.5 (1.8–4.3)4.1 (2.1–7.1)ECOG PS ≥2 at start of 2L57 (9.1)13 (12.9)15 (6.8)16 (14.4)CNS/brain metastases at start of 2L80 (12.8)14 (13.9)21 (9.5)16 (14.4)Median TTNT‡, mo (95% CI)4.5 (4.1–5.0)4.1 (3.5–5.0)5.5 (4.4–6.2)4.1 (3.1–4.8)Median OS‡, mo (95% CI)10.2 (8.9–11.1)10.0 (8.0–13.5)12.4 (10.6–15.0)8.3 (6.9–9.6)1-y OS‡, % (95% CI)42.3 (38.2–46.4)43.6 (33.3–53.8)51.9 (45.2–58.7)29.3 (20.1–38.6)TFI=treatment-free interval. *Any regimen containing each agent (monotherapy or combination); subgroups not mutually exclusive. †Defined as the interval between last (neo)adjuvant therapy and metastatic diagnosis; percentages calculated using pts with recurrent disease and non-missing TFI as the denominator. ‡From start of 2L Conclusions: There was no clear 2L treatment standard used for mTNBC and median OS was short (10.2 mo overall). Notably, pts receiving 2L gemcitabine- vs taxane-containing therapy experienced shorter median OS and lower 1-y OS rates, although imbalances in prior therapy, disease biology, and demographic and prognostic factors between these subgroups may have contributed to the observed differences. 2L treatment for mTNBC remains an area of high unmet medical need. Citation Format: Luhn P, O'Hear C, Ton TG, Hsieh A, Yi J, Chang C-W, Funke R, Kurian A. Outcomes in patients (pts) with metastatic triple-negative breast cancer (mTNBC) treated in second line (2L) in the US real-world setting [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-14-04.

Background: Neoadjuvant endocrine therapy (NET) has long been limited to patients who were deemed medically unfit for immediate surgery or on clinical trials. Coronavirus disease 2019 (COVID-19) resulted in a global pandemic, which led to deferral of elective surgeries including breast surgeries for early stage breast cancer patients during March - June 2020. Institutional guidelines were developed based on societal recommendations, including NCCN, to use NET as a bridge to surgery. Objective: Primary objective was to establish a database of early stage HR+ Her2/neu- breast cancer patients diagnosed during COVID-19 who were treated with NET as a bridge to surgery. Secondary endpoints include correlation between duration of NET and changes in pathological variables. Method: This was a single institution, retrospective observational study from Perlmutter Cancer Center at NYU Langone Hospital and NYU Langone Hospital - Long Island of DCIS and early stage breast cancer patients diagnosed from March 15, 2020 - June 1, 2020 during COVID-19 pandemic. Inclusion criteria were males and females older than 18 years of age and initial diagnosis of DCIS or early stage HR+ Her2/neu- breast cancer who did not require neoadjuvant chemotherapy by established guidelines. Descriptive statistics were calculated separately by DCIS and invasive breast cancer using SAS version 9.4. Results: From March 15 - June 1, 2020, 13 patients who were diagnosed with DCIS and 41 patients with early stage HR+ Her2/neu- invasive breast cancer received NET (Table 1). Of the 41 patients with invasive breast cancer, 19 (46%) had Oncotype DX assay on biopsy specimens; 12/19 (63%) had scores 10-14 and 7/19 (37%) had scores 15-25. 38/41 (92.7%) had post-surgery Ki-67% and 16/38 (42.1%) demonstrated maturation arrest (Ki-67 <2.7%). 26/41 (63%) invasive breast cancer patients had pre and post Ki-67% checked while on aromatase inhibitors (AI); 21/26 (81%) had a decrease in Ki-67%, 2/26 (7.7%) patients had no change, and 3/26 (11.5%) had an increase. Of those 21 patients, the percent change of Ki-67% from baseline was mean 69.15% ± 22.58 and median 71.83%. No significant associations with changes (pre to post) in Ki-67%, T stage, ER% and PR% in NET for ≤4 weeks and >4 weeks (Table 2). Median duration of NET in invasive breast cancer was 6.85 weeks. 1 patient had a complete pathological response after NET and 2 patients were upstaged from DCIS to invasive carcinoma at the time of surgery. Conclusion: While the sample sizes are small, this is a unique cohort of early stage surgically resectable breast cancer patients who were treated with NET during the COVID-19 pandemic. This real-world data confirms pathological changes, especially decrease in Ki-67% even with short duration use of NET that has been reported in trials of neoadjuvant AI. Long term follow-up for survival outcome is planned. Table 1.Demographics of early stage breast cancer patients diagnosed during COVID-19.DCIS (n=13)Invasive Breast Cancer (n=41)Total (n=54)Menopause status (n, %)Pre-menopause7 (53.8)6 (14.6)13 (24.1)Post-menopause6 (46.2)35 (85.4)41 (75.9)Diagnosis (n, %)Self-Palpated08 (19.5)8 (14.8)Screening13 (100)33 (80.5)46 (85.2)Age (n, %)≤503 (23.1)5 (12.2)8 (14.8)50+10 (76.9)36 (87.8)46 (85.2)Clinical Stage (n, %)Tis13 (100)013 (24.1)I037 (90.2)37 (68.5)II04 (9.8)4 (7.4)NET in weeks (n, %)≤43 (23.1)11 (26.8)14 (25.9)4+10 (76.9)30 (73.2)40 (74.1)Genomic Testing (n, %)Oncotype DX019 (86.4)19 (86.4)ProSigna03 (13.6)3 (13.6)Mammaprint000 Table 2.No significant associations with changes in pre to post in T stage, ER%, PR% or Ki-67% in patients treated with NET for ≤4 weeks and >4 weeks.≤4 weeks>4 weeksp-valueChange in T stage0.5810Decrease2 (27.27%)8 (26.67%)No change7 (63.64%)15 (50%)Increase1 (9.09%)7 (23.33%)Change in ER%0.2444Decrease4 (36.36%)9 (30%)No change4 (36.36%)5 (16.67%)Increase3 (27.27%)16 (53.33%)Change in PR%1.0000Decrease7 (70%)21 (70%)No change2 (20%)5 (16.67%)Increase1 (10%)4 (13.33%)Change in Ki-67%0.3224Decrease4 (66.67%)17 (85%)No Change1 (16.67%)1 (5%)Increase1 (16.67%)2 (10%) Citation Format: Julie Huang, Joshua Feinberg, Bahram Dabiri, Jordan Baum, Meredith Akerman, Anthony Pasquarella, Abhinav Rohatgi, Shubhada Dhage, Amber Guth, Nina D'Abreo. Neoadjuvant endocrine therapy (NET) as bridge therapy for early stage breast cancer during COVID-19: A single institution experience [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-15-03.

Background Anthracyclines and taxanes are chemotherapeutic agents widely used in a sequential regimen in the adjuvant and neoadjuvant treatment of early breast cancer to reduce the risk of cancer recurrence. Standard practice is to administer anthracycline-based chemotherapy followed by a taxane. Anthracyclines tend to be administered first as they were established before taxanes for treatment of early breast cancer. Objectives To assess whether the sequence in which anthracyclines and taxanes are administered affects outcomes for people with early breast cancer receiving adjuvant or neoadjuvant therapy. Search methods We searched Cochrane Breast Cancer's Specialised Register, CENTRAL, MEDLINE, Embase, the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov on 1 February 2018. Selection criteria Randomised controlled trials comparing administering a taxane prior to an anthracycline with taxane following anthracycline to people with early breast cancer receiving chemotherapy. The studies needed to have reported on at least one of our outcomes of interest, which included overall survival, disease-free survival, pathological response, treatment adherence, toxicity and quality of life. Data collection and analysis Two review authors independently extracted data, assessed risk of bias and quality of the evidence. The primary outcome measure was overall survival. Secondary outcomes included disease-free survival, pathological response (in the neoadjuvant setting only), adverse events, treatment adherence and quality of life. For time-to-event outcomes of overall survival and disease-free survival, we derived hazard ratios (HRs) with 95% confidence intervals (CI) where possible. For dichotomous outcomes of pathological complete response, treatment adherence and adverse events, we reported the treatment effect as a risk ratio (RR) with 95% CI where possible. We used GRADE to assess the certainty of the evidence separately for the neoadjuvant and adjuvant settings. Main results There were 1415 participants in five neoadjuvant studies and 280 participants in four adjuvant studies involving five treatment comparisons. Four of the five neoadjuvant studies collected data for the primary outcome (overall survival) and two studies had data available; one of the four adjuvant studies collected overall survival data.The neoadjuvant studies suggested that the administration of taxanes first probably resulted in little to no difference in overall survival (HR 0.80, 95% CI 0.60 to 1.08; 947 participants; 2 studies; moderate-certainty evidence) and disease-free survival (HR 0.84, 95% CI 0.65 to 1.09; 828 participants; 1 study; moderate-certainty evidence). Administration of taxanes first also resulted in little to no difference in pathological complete response (absence of cancer in the breast and axilla: RR 1.15, 95% CI 0.96 to 1.38; 1280 participants; 4 studies; high-certainty evidence). However, there appeared to be a trend in favour of taxanes first. Studies reported treatment adherence using a range of measures. Administration of taxanes first probably did not increase the likelihood of requiring dose reductions compared to administration of anthracyclines first (RR 0.81, 95% CI 0.59 to 1.11; 280 participants; 1 study; moderate-certainty evidence). There was probably little to no difference in the risk of grade 3/4 neutropenia (RR 1.25, 95% CI 0.86 to 1.82; 280 participants, 1 study; moderate-certainty evidence) or grade 3/4 neurotoxicity (RR 0.95, 95% CI 0.55 to 1.65; 1108 participants; 2 studies; low-certainty evidence) when taxanes were given first. There were no data on quality of life.Only one adjuvant study collected data on overall survival and disease-free survival but did not report data. Administration of taxanes first reduced the risk of grade 3/4 neutropenia (RR 0.62, 95% CI 0.40 to 0.97; 279 participants; 4 studies, 5 treatment comparisons; high-certainty evidence) and appeared to result in little to no difference in grade 3/4 neurotoxicity (RR 0.78, 95% CI 0.25 to 2.46; 162 participants; 3 studies; low-certainty evidence). There was probably little to no difference in the proportions experiencing dose delays when taxanes are given first compared to anthracyclines given first (RR 0.76, 95% CI 0.52 to 1.12; 238 participants; 3 studies, 4 treatment comparisons; moderate-certainty evidence). One study reported on quality of life and indicated that scores (using the Functional Assessment of Cancer Therapy - Breast Cancer (FACT-B) validated questionnaire) were similar in both groups though did not provide numerical data. Authors' conclusions In the neoadjuvant setting, there is high- to low-certainty evidence of equivalent outcomes for the sequence in which taxanes are delivered. In the adjuvant setting, none of the studies reported on overall survival or disease-free survival. In most institutions, standard practice would be to deliver anthracycline followed by taxane, and currently available data do not support a change in this practice. We wait for the full-text publication of a relevant neoadjuvant study for women with HER2-negative breast cancer for inclusion in an update of this review.

Elucidating the Role of Chest Wall Irradiation in ‘Intermediate-risk’ Breast Cancer: the MRC/EORTC SUPREMO Trial

The 41st San Antonio Breast Cancer Symposium was held in San Antonio, Texas, USA on December 4-8, 2018. In this article, we reviewed the key advancement in breast cancer surgery, chemotherapy, targeted therapy, immunotherapy and endocrine therapy reported in this symposium, in order to provide references for clinicians in the treatment and research of breast cancer. The 10-year follow-up data of the EORTC AMAROS study suggested that axillary radiotherapy was a safe and feasible alternative to axillary lymph node dissection for primary breast cancer patients with positive axillary lymph nodes confirmed by sentinel lymph node biopsy. The result of the phase 3 GEICAM/CIBOMA study showed that in early triple negative breast cancer patients, capecitabine administration after surgery and standard chemotherapy did not significantly improve the patients’ survival. The meta-analysis conducted by researchers in Harvard University suggested that the patients who achieve pCR after neoadjuvant chemotherapy could be exempted from conventional adjuvant chemotherapy, with no obvious effect on patients’ survival. The multi-center PEONY study conducted by Professor Shao Zhimin in China showed that for neoadjuvant therapy of early or locally advanced HER-2 positive breast cancer patients in Asia, the overall postoperative pCR rate of double-target group (pertuzumab monoclonal antibody + trastuzumab monoclonal antibody + docetaxel) was significantly higher than that of single-target group (trastuzumab monoclonal antibody + docetaxel). The KATHERINE study showed that the trastuzumab monoclonal antibody combined with maitansine conjugate was feasible in the adjuvant treatment of HER-2 positive early breast cancer. An exploratory analysis to evaluate the efficacy of immuno-biomarker subgroups in the IMpassion 130 study showed that the patients with programmed death ligand 1 positive in immunocytes significantly benefited from the treatment of atezolizumab monoclonal antibody + albumin paclitaxel. The PALLET study showed that in postmenopausal early breast cancer patients with ER positive and HER-2 negative, the neoadjuvant endocrine therapy of letrozole combined with CDK4/6 inhibitors significantly increased the inhibition rate of Ki67, but did not improve the clinical response rate. The 10-year clinical data of the AERAS study showed that the patients significantly benefited from the adjuvant endocrine therapy if the use of anastrozole was extended to 10 years. The meta-analysis of EBCTCG showed that prolonged endocrine therapy significantly reduced the overall risk of recurrence in hormone receptor-positive postmenopausal breast cancer. The TAM-01 study suggested that low-dose administration of tamoxifen could reduce the toxicity and improve the efficacy in patients with breast intraductal neoplasms. The clinicians should actively promote the clinical research of new drugs and the exploratory analysis of predictive biomarkers, take the advantages of domestic researches and learn advanced techniques and concepts overseas in order to benefit most of breast cancer patients. Key words: Breast neoplasms; Endocrine therapy; Triple negative breast cancer; Neoadjuvant therapy; Immunotherapy

Epidemiology and Its Lessons.- Diet and Mammary Gland Carcinogenesis. Prevention of Breast Cancer: Focus on Chemoprevention. Estrogen/Hormone Replacement Therapy and the Etiology of Breast Cancer. Genetics of Breast Cancer.- Experimental Pathology and Breast Cancer Genetics: New Technologies. Update on Breast Cancer Susceptibility Genes. Biology of Breast Cancer.- IGF-I Physiology and Breast Cancer. Determination of Clinical Utility of Tumor Markers: A Tumor Marker Utility Grading System. How Can Prognostic and Predictive Factors in Breast Cancer be Used in a Practical Way Today?. Strategies for the Development of Vaccines to Treat Breast Cancer. In Situ Breast Cancer.- Hypothesis and Practice: Are There Several Types of Treatment for Ductal Carcinoma in Situ of the Breast?. Ductal Carcinoma in Situ of the Breast: Histological Classification and Genetic Alterations. Trials of Treatment for Non-invasive Breast Cancer. Summary. Controversies About the Axilla.- The Axilla: To Clear or Not to Clear? That is the Question!. Axillary Clearance in Operable Breast Cancer: Still a Necessity?. Sentinel Lymphadenectomy: A Safe Answer to Less Axillary Surgery?. Endoscopic Surgery To the Axilla: A Substitute for Conventional Axillary Clearance?. Integrated Therapy: Changing Surgical Procedures for Breast Cancer.- Surgical Considerations in Preoperative Chemotherapy of Breast Cancer. Integration of Plastic Surgery in the Course of Breast-Conserving Surgery for Cancer to Improve Cosmetic Result and Radicality of Tumor Excision. Summary. Integrated Therapy: Primary Adjuvant Systemic Therapy.- Is Primary Chemotherapy Useful for All Patients with Primary Invasive Breast Cancer?. The Primary Use of Endocrine Therapies. Integrated Therapy: Radiation Therapy/Endocrine Treatment.- When and How to Combine Chemotherapy and Radiation Therapy in Breast Cancer Patients. Novel Approaches Using Radiation Therapies. Molecular Biology of the Estrogen Receptor Aids in the Understanding of TamoxifenResistance and Breast Cancer Prevention with Raloxifene. Aromatase Inhibitors and Their Use in the Adjuvant Setting. GnRH Analogues and Ovarian Ablation: Their Integration in the Adjuvant Strategy. Summary. Adjuvant Systemic Treatments: Cytotoxic Strategies.- Putting the Taxanes to Work: Unanswered Questions. Putting Taxanes to Work in Operable Breast Cancer: A Search for Selective Indications from Empirical Studies. Continous Infusional Chemotherapy for Early Breast Cancer: The Royal Marsden Hospital Experience. Tailored Chemotherapy to Equal Toxicity: Is It Possible?. Anti-angiogenesis Therapy and Strategies for Integrating It with Adjuvant Therapy. Adjuvant Systemic Treatments: Cytotoxics and Their Dosage.- New Developments in High-Dose Chemotherapy for Breast Cancer. Summary. Adjuvant Systemic Treatments: Quality of Life.- Quality of Life Assessment in the Adjuvant Setting: Is It Relevant?. Quality of Life Assessment in the International Breast Cancer Study Group: Past, Present, and Future. Impact of Different Adjuvant Therapy Strategies on Quality of Life in Breast Cancer Survivors. Summary. Clinical Research Around the World: Review of Cooperative Group Trials.- North American Adjuvant Breast Cancer Trials. International Breast Cancer Study Group Trials. Nordic Trials of Adjuvant Therapy in Primary Breast Cancer. The EORTC-Breast Cancer Cooperative Group Clinical Research Programme in Early Breast Cancer. Italian Breast Cancer Adjuvant Chemo-hormone Therapy Cooperative Group Trials. Current Trials of the German Adjuvant Breast Cancer Group (GABG). International Consensus Conference on Primary Treatment of the Breast: Update 1998.- International Consensus Panel on the Treatment of Primary Breast Cancer V: Update 1998. Subject Index.-