Sequencing of Tamoxifen and Radiotherapy After Breast-Conserving Surgery in Early-Stage Breast Cancer

2005 ◽  
Vol 23 (1) ◽  
pp. 24-29 ◽  
Author(s):  
Lori J. Pierce ◽  
Laura F. Hutchins ◽  
Stephanie R. Green ◽  
Danika L. Lew ◽  
Julie R. Gralow ◽  
...  

Purpose Tamoxifen (TAM) is thought to exert a cytostatic effect on hormone-sensitive breast cancer cells. Some preclinical studies show reduced radiosensitivity in irradiated malignant mammary epithelial cells when pretreated with TAM; other studies refute these results. Recent randomized clinical trials suggest an antagonistic effect of TAM on cytotoxic therapy, with improved disease-free survival (DFS) with sequential versus concurrent TAM. An exploratory analysis was undertaken to evaluate the optimal sequencing of TAM and radiotherapy (RT) after breast-conserving surgery. Patients and Methods Southwest Oncology Group trial 8897 (Intergroup 0102) randomly assigned node-negative women with T1-3 breast cancers to cyclophosphamide, doxorubicin, fluorouracil (CAF); CAF → TAM; cyclophosphamide, methotrexate, fluorouracil (CMF); and CMF → TAM. For this analysis, data are reported only in the TAM groups. RT was allowed either before adjuvant therapy (sequential [SEQ] RT; 107 patients) or after chemotherapy but concurrent with TAM (concurrent [CONC] RT; 202 patients). Survival data were adjusted for receptor status, age, and tumor size. Results With a median follow-up of 10.3 years, 10-year DFS values were 83% and 83% for CONC versus SEQ RT groups (log-rank P = .73; P = .76 adjusted for patient characteristics), and 10-year overall survivals were 88% and 90%, respectively (log-rank P = .59; adjusted P = .65). Patterns of failure showed no increase in in-breast recurrence rates between CONC RT and SEQ RT groups, with 10-year local recurrence rates of 7% for CONC RT and 5% for SEQ RT (hazard ratio, 0.73; 95% CI, 0.26 to 2.04; P = .54). Conclusion The current analysis does not suggest an adverse effect on local or systemic control with CONC versus SEQ TAM and RT in node-negative breast cancer. A randomized trial is encouraged to validate these results.

2021 ◽  
Author(s):  
Omer Diker ◽  
Burak Yasin Aktas ◽  
Recep Ak ◽  
Bahadır Koylu ◽  
Onur Bas ◽  
...  

Background: In node-negative HER2-overexpressed breast cancers, adjuvant paclitaxel plus trastuzumab treatment is a successful de-escalation approach with excellent survival outcomes. Methods: All patients with HER2+ breast cancer treated in our centers were retrospectively reviewed. Results: We analyzed 173 patients who were treated with adjuvant paclitaxel plus trastuzumab. The mean tumor size was 2.2 cm. There were eight invasive disease events or death: four distant recurrences (2.3%), three locoregional recurrences (1.7%) and one death without documented recurrence after a 52 month follow-up. The 3-year disease-free survival and recurrence-free interval rate was 96.6%. Conclusion: This real-life experience with adjuvant paclitaxel plus trastuzumab demonstrated few distant recurrences and is compatible with the APT trial findings.


2020 ◽  
Vol 86 (10) ◽  
pp. 1248-1253
Author(s):  
Sarah Walcott-Sapp ◽  
Marissa K. Srour ◽  
Minna Lee ◽  
Michael Luu ◽  
Farin Amersi ◽  
...  

Optimum tissue resection volume for patients with invasive breast cancer undergoing breast conserving surgery following neoadjuvant therapy (NAT) is not known. We compared positive margin and in-breast tumor recurrence (IBTR) between 2 groups that were created based on radiologic tumor size (RTS (cm3)) at diagnosis, RTS post-NAT, and volume of tissue resected (VTL): Pre-NAT group, patients with VTL closer to RTS at diagnosis, and post-NAT group, patients with VTL closer to post-NAT RTS. 82 patients with 84 breast cancers treated with NAT between 2007 and 2017 who had pre- and post-NAT imaging were identified from a prospectively maintained database. RTS at diagnosis, RTS post-NAT, and VTL were determined. Clinical and treatment characteristics, IBTR, and disease-free survival (DFS) were compared between pre-NAT (n = 51) and post-NAT (n = 33) groups. Compared to post-NAT patients, pre-NAT patients had smaller RTS at presentation (9.2 vs. 33.5 cm3, P < .001) and post-NAT (1.2 vs. 8.2 cm3, P = .024). At median follow-up of 4 years, there were no differences between groups in pathologic tumor size, positive margin rate, adjuvant therapy, IBTR, or DFS. Resection volumes that matched RTS on post-NAT imaging were not associated with increased positive margins or IBTR. It may be appropriate to use post-NAT imaging to guide lumpectomy volume.


Author(s):  
Lorena Gonzalez ◽  
Joanne Mortimer ◽  
Laura Kruper

Abstract Purpose of Review This review summarizes the most recent data on the management of small, node-negative Her2+ and triple-negative breast cancer. Recent Findings Both Her2+ and triple-negative breast cancers are characterized by high rates of recurrence and worse survival outcomes compared to hormone-positive cancers. De-escalation of systemic therapy in early-stage breast cancer is a recent national trend in clinical research. Recent prospective trials support the scaling back of cytotoxic agents and maximization of targeted therapy regimens. Similarly, large retrospective studies on small, node-negative triple-negative breast cancer report the omission of chemotherapy in women with T1a,N0 triple-negative cancers with favorable short term outcomes. Summary De-escalation of systemic therapy for Her2+ breast cancer is effective in the management of early-stage, node-negative disease. Future prospective studies on the omission of systemic therapy for triple-negative breast cancer are required to safely adopt into consensus guidelines.


2020 ◽  
Vol 18 (7.5) ◽  
pp. 937-940
Author(s):  
Benjamin O. Anderson ◽  
Janice A. Lyons

Locoregional management of early-stage breast cancer has been trending toward less-extensive axillary resections, based on increasing evidence showing that patients with 1 or 2 positive sentinel nodes and/or micrometastases can safely be managed with sentinel node biopsy alone, thereby avoiding complete axillary lymph node dissection (cALND) in the significant majority of patients. Because of the 15% to 20% lymphedema risk associated with cALND, increasing efforts are being made to avoid the procedure when evidence suggests that more limited procedures are safe, as reflected by acceptable locoregional recurrence rates. Axillary radiotherapy (RT) has been shown to be an effective alternative to ALND for patients fitting criteria from the pivotal AMAROS trial: patients with T1/T2 disease and are clinically node-negative, who undergo either breast-conserving therapy or mastectomy. Considerations for RT begin with the question of nodal involvement, with treatment planned accordingly. With more neoadjuvant therapy being used, there are nuances in locoregional management that clinicians must now appreciate, both in terms of ALND and axillary RT.


2021 ◽  
Vol 20 (4) ◽  
pp. 116-121
Author(s):  
A. R. Bosieva ◽  
M. V. Ermoshchenkova ◽  
N. N. Volchenko ◽  
A. D. Zikiryahodjaev

The purpose of the study was to present the most recent data on the outcomes of breast-conserving surgery after neoadjuvant chemotherapy for breast cancer patients.Material and methods. We analyzed relevant publications available in the pubmed, cochrane library, e-library databases between 1990 and 2020, and 24 of them were used to write this review.Results. Neoadjuvant chemotherapy for breast cancer patients is currently a widespread treatment option. The main advantage of this type of treatment for patients with early stage breast cancer is the feasibility of performing breast-conserving surgery in cases of partial or complete clinical response and, therefore, the improvement of the quality of life of patients with equivalent rates of disease-free survival compared to radical mastectomies.Conclusion. Numerous studies have shown that breast-conserving surgery following neoadjuvant chemotherapy is the safe surgery with good oncologic outcomes and an alternative to radical mastectomies in breast cancer patients. However, further studies are required to determine the optimal safe resection margin width in patients with complete and partial responses to neoadjuvant chemotherapy.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e12002-e12002
Author(s):  
Robert W. Galamaga ◽  
Rachel Mariani ◽  
Imad Almanaseer ◽  
Jacob D. Bitran

e12002 Background: Human epidermal growth factor receptor 2 (HER-2) overexpression occurs in up to 30% of breast cancers and has been associated with poor clinical outcomes that have improved with advances in HER-2 directed therapy. The HER-2 gene resides on the long arm of chromosome 17 and amplification is typically assessed via immunohistochemistry or fluorescence in situ hybridization (FISH); HER-2 is interpreted as amplified, non-amplified, or equivocal. The effect and clinical impact of chromosome 17 polysomy in specimens interpreted as HER-2 non-amplified has not been well-established in breast cancer patients. This subgroup may represent a unique set of patients who may benefit from HER-2 directed therapy given the increase in HER-2 gene copy number. If tumors with polysomy 17 share biologic similarities with those positive for HER-2 amplification this may significantly influence the approach to treating these patients. In a single institution study we reviewed all breast cancer cases diagnosed in 2008 which were reported as HER-2 equivocal or non-amplified via FISH and with chromosome 17 polysomy in order to extrapolate disease-free and overall survival data within this subset. Methods: HER-2 expression via FISH from patients diagnosed with breast cancer in 2008 was reviewed. In those patients with equivocal or non-amplified HER-2 expression we selected those with chromosome 17 polysomy defined as a chromosome 17 centromere copy number of > 3 per tumor cell. A total of 9 patients were identified. Results: The median age was 74 (36-88). Median tumor size was 1.6 cm (0.7-4.9) and 8 patients (88%) had both estrogen and progesterone positive tumors. Stage distribution was as follows: stage IA: 4 (44%); stage IIA: 2 (22%); stage IIB: 2 (22%) and stage IIIA: 1 (11%). The actuarial 3 year disease free survival was 67%. Conclusions: Breast cancers with equivocal or non-amplified HER-2 expression with chromosome 17 polysomy represent a unique subset of tumors with a biology that is not well-understood. Previously published studies have yielded conflicting results regarding the prognostic significance of this genotype. Our study reflects a three year survival of 67% which suggests that these patients represent an aggressive subset.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 576-576
Author(s):  
Katherine Clifton ◽  
Angelica Gutierrez Barrera ◽  
Junsheng Ma ◽  
Roland L. Bassett ◽  
Jennifer Keating Litton ◽  
...  

576 Background: NSABP Protocol B-18 was a randomized trial which found no statistically significant difference in overall survival (OS) in patients (pts) receiving neoadjuvant (NAC) or adjuvant chemotherapy (AC), however outcome was not analyzed by breast cancer subtypes. Subsequent retrospective studies in TNBC reported conflicting results with an initial study showing a significant OS benefit with AC and later studies showing a trend toward improved survival with NAC. Furthermore, studies have not included a significant number of pts with BRCA mutations. This study aims to analyze outcomes of AC versus NAC in pts with early stage TNBC with and without BRCA germline mutations. Methods: Pts with stage I or II TNBC who had BRCA testing were identified from a prospective cohort study of 4027 pts at MD Anderson Cancer Center. Clinical, demographic, genetic test results, chemotherapy, recurrence, survival data were collected. OS and disease free survival (DFS) were estimated using the Kaplan-Meier method, and log-rank tests were used to compare groups. Results: 305 pts with stage I and II TNBC who met eligibility criteria were included in the analysis. Pts who received both NAC and AC or no chemotherapy were excluded. 181 received AC (59.3%) and 124 received NAC (40.7%). The majority of the pts were less than 50 years old (236, 77.4%) and white (194, 63.8%). 134 were BRCA positive (44.1%) and 170 were BRCA negative (55.9%). The majority of the pts received an anthracycline and taxane regimen (223, 73.1%). There was no significant association between OS or DFS and treatment with NAC versus AC in the overall cohort. Furthermore, there were no significant differences between pt subgroups (NAC BRCA positive, NAC BRCA negative, AC BRCA positive, and AC BRCA negative) with respect to either OS or DFS. Conclusions: NAC versus AC with standard anthracycline and taxane containing regimens results in similar DFS and OS survival amongst pts with stage I and II TNBC regardless of BRCA status. Further studies are needed to evaluate whether similar results are observed with newer agents, such as platinums, PARP inhibitors and other targeted agents.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xingfa Huo ◽  
Jinming Li ◽  
Fuxing Zhao ◽  
Dengfeng Ren ◽  
Raees Ahmad ◽  
...  

Abstract Background The role of capecitabine in neoadjuvant and adjuvant chemotherapy for early-stage triple-negative breast cancer (TNBC) is highly controversial. Our meta-analysis was designed to further elucidate the effects of capecitabine on survival in early-stage TNBC patients and its safety. Methods PubMed, Embase, and papers presented at several main conferences were searched up to December 19, 2019, to investigate capecitabine-based versus capecitabine-free neoadjuvant and adjuvant chemotherapy in TNBC patients. Heterogeneity was assessed using I2 test, combined with hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI) computed for disease-free survival (DFS), overall survival (OS), and over grade 3 adverse events (AEs). Results A total of 9 randomized clinical trials and 3842 TNBC patients were included. Overall, the combined capecitabine regimens in neoadjuvant and adjuvant chemotherapy showed significantly improved DFS (HR = 0.75; 95% CI, 0.65–0.86; P < 0.001) and OS (HR = 0.63; 95% CI, 0.53–0.77; P < 0.001). In subgroup analysis, there were improvements in DFS in the groups with addition of capecitabine (HR = 0.64; 95% CI, 0.53–0.78; P < 0.001), adjuvant chemotherapy (HR = 0.73; 95% CI, 0.63–0.85; P < 0.001), and lymph node positivity (HR = 0.62; 95% CI, 0.44–0.86; P = 0.005). Capecitabine regimens were related to higher risks of diarrhea (OR = 2.88, 95% CI 2.23–3.74, P < 0.001), stomatitis (OR = 2.01, 95% CI 1.53–2.64, P < 0.001) and hand–foot syndrome (OR = 8.67, 95% CI 6.70–11.22, P < 0.001). Conclusion This meta-analysis showed that neoadjuvant and adjuvant chemotherapy combined with capecitabine significantly improved both DFS and OS in early-stage TNBC patients with tolerable AEs. There were benefits to DFS in the groups with the addition of capecitabine, adjuvant chemotherapy, and lymph node positivity.


2007 ◽  
Vol 25 (6) ◽  
pp. 656-661 ◽  
Author(s):  
Hannah M. Linden ◽  
Charles M. Haskell ◽  
Stephanie J. Green ◽  
C. Kent Osborne ◽  
George W. Sledge ◽  
...  

Purpose We conducted a phase III randomized study of two adjuvant treatment schedules of doxorubicin (A) and cyclophosphamide (C) in early-stage breast cancer to determine if administration of sequential single agents (A → C) results in superior disease-free survival (DFS) and overall survival (OS) versus the same total dose given in combination (AC). Patients and Methods High-risk node-negative or low-risk node-positive breast cancer patients received AC given: (arm I) concurrently (AC) doxorubicin 54 mg/m2 and cyclophosphamide 1.2 g/m2 intravenously (IV) every 3 weeks for six cycles; or (arm II) in sequence (A → C) doxorubicin 40.5 mg/m2 IV days 1 and 2 every 3 weeks for four cyles followed by cyclophosphamide 2.4 gm/m2 IV every 2 weeks for three cycles. Total dose and duration were identical, but the intensity of each drug was increased on A → C. Both arms included granulocyte colony-stimulating factor support and prophylactic antibiotics. All but premenopausal women with receptor negative tumors received tamoxifen after chemotherapy. Results Between 1994 and 1997, 3,176 patients were randomly assigned. Arms were well balanced; 48% of eligible patients were node-negative and 48% were estrogen receptor–positive. No significant differences in OS or DFS were observed; 5-year estimates of OS (95% CI) were 88% (87% to 90%) on AC and 89% (87% to 91%) on A → C. Grade 4 hematologic toxicity was greater on A → C, but nonhematological grade 4 was similar. Conclusion The overall result does not support superiority of dose-intense sequenced single agents. The greater toxicity of higher doses of single agents does not support their sequential use.


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