scholarly journals Optimal systemic therapy for early breast cancer in women: a clinical practice guideline

2014 ◽  
Vol 22 ◽  
pp. 67 ◽  
Author(s):  
A. Eisen ◽  
G.G. Fletcher ◽  
S. Gandhi ◽  
M. Mates ◽  
O.C. Freedman ◽  
...  

The Breast Cancer Disease Site Group of Cancer Care Ontario identified the need for new guidelines for the adjuvant systemic therapy of early-stage breast cancer. The specific question to be addressed was “What is the optimal adjuvant systemic therapy for female patients with early-stage operable breast cancer, when patient and disease factors are considered?”A systematic review was prepared based on literature searches conducted using the medline and embase databases for the period January 2008 to March 5, 2012, and updated to May 12, 2014. Guidelines were located from that search, from the Standards and Guidelines Evidence directory of cancer guidelines, and from the Web sites of major guideline organizations. The literature located was subdivided into the broad categories of chemotherapy, hormonal therapy, and therapy targeted to her2 (human epidermal growth factor receptor 2). Although several of the systemic therapies discussed in this guideline can be considered in the neoadjuvant setting, the review focused on trials with rates of disease-free and overall survival as endpoints and thus excluded several trials that used pathologic complete response as a primary endpoint.Based on the systematic review, the working group drafted recommendations on the use of chemotherapy, hormonal therapy, and targeted therapy; based on their professional experience, they also drafted recommendations on patient and disease characteristics and recurrence risk. The literature review and draft recommendations were circulated to a consensus panel of medical oncologists who had expertise in breast cancer and who represented the regions of Ontario. Items without initial consensus were discussed at an in-person consensus meeting held in Toronto, November 23, 2012. The final recommendations are those for which consensus was reached before or at the meeting. Some of the key evidence was revised after the updated literature search. Evidence reviews for systemic chemotherapy, endocrine therapy, and targeted therapy for her2-positive disease are reported in separate articles in this supplement. The full three-part 1-21 evidence-based series, including complete details of the development and consensus processes, can be found on the Cancer Care Ontario Web site at https://www.cancercare.on.ca/toolbox/qualityguidelines/diseasesite/breast-ebs.

2020 ◽  
Author(s):  
Sara A Hurvitz ◽  
Jennifer L Caswell-Jin ◽  
Katherine L McNamara ◽  
Jason Zoeller ◽  
Gregory R Bean ◽  
...  

In this neoadjuvant trial (TRIO-US B07), participants with early-stage HER2-positive breast cancer (N=128) were randomized to receive trastuzumab (T), lapatinib (L), or both (TL) as HER2-targeted therapy, with each participant given one cycle of this designated anti-HER2 therapy alone followed by six cycles of standard combination chemotherapy with the same anti-HER2 therapy. We observed similar pathologic complete response (pCR) rates between T and TL, and a lower pCR rate with L. Higher-level amplification of HER2 and hormone receptor-negative status were associated with a higher pCR rate. Higher pre-treatment immune infiltrate trended toward higher pCR rate in T-treated groups, and greater HR expression correlated with lower immune infiltrate. Large shifts in tumor, immune, and stromal gene expression occurred after one cycle of HER2-targeted therapy. In contrast to pCR rates, the L-containing arms exhibited greater proliferation reduction than T at this timepoint. Immune expression signatures increased in all arms after one cycle of HER2-targeted therapy, decreasing again by the time of surgery. Our results inform approaches to early assessment of sensitivity to anti-HER2 therapy and shed light on the role of the immune microenvironment in response to HER2-targeted agents.


1997 ◽  
Vol 15 (6) ◽  
pp. 2338-2344 ◽  
Author(s):  
E Guadagnoli ◽  
C Shapiro ◽  
J H Gurwitz ◽  
R A Silliman ◽  
J C Weeks ◽  
...  

PURPOSE To assess whether the use of adjuvant systemic therapy in postmenopausal women with early-stage breast cancer is influenced by patient age. METHODS A retrospective cohort study based on data collected from medical records and from patients and their surgeons was performed among 746 postmenopausal patients diagnosed with early-stage breast cancer at 30 hospitals located throughout Minnesota. The adjusted odds of receiving hormonal therapy, chemotherapy, and both hormonal therapy and chemotherapy as a function of age was determined. RESULTS Among women with negative lymph nodes, 62% received some form of adjuvant drug therapy. For these women, the likelihood of receiving hormonal therapy or both hormonal therapy and chemotherapy did not vary with patient age and the likelihood of receiving chemotherapy declined with age. Among women with positive lymph nodes, 92% received some form of adjuvant therapy. For these women, the likelihood of receiving hormonal therapy increased with age and the likelihood of receiving chemotherapy declined with age, as did the likelihood of receiving both hormonal therapy and chemotherapy. CONCLUSION The observed associations between age and the use of adjuvant systemic therapy appear to reflect, in general, available information about treatment efficacy and do not suggest underuse among elderly women with early-stage breast cancer. The use of adjuvant therapy depends on clinical factors that predict the increased risk of metastases or the increased likelihood of response to treatment, rather than other sociodemographic factors. Our results also suggest that younger postmenopausal women with positive lymph nodes compared with older women may be undertreated with respect to tamoxifen because of the substitution of chemotherapy for hormonal therapy.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Sara A. Hurvitz ◽  
Jennifer L. Caswell-Jin ◽  
Katherine L. McNamara ◽  
Jason J. Zoeller ◽  
Gregory R. Bean ◽  
...  

AbstractIn this multicenter, open-label, randomized phase II investigator-sponsored neoadjuvant trial with funding provided by Sanofi and GlaxoSmithKline (TRIO-US B07, Clinical Trials NCT00769470), participants with early-stage HER2-positive breast cancer (N = 128) were recruited from 13 United States oncology centers throughout the Translational Research in Oncology network. Participants were randomized to receive trastuzumab (T; N = 34), lapatinib (L; N = 36), or both (TL; N = 58) as HER2-targeted therapy, with each participant given one cycle of this designated anti-HER2 therapy alone followed by six cycles of standard combination chemotherapy with the same anti-HER2 therapy. The primary objective was to estimate the rate of pathologic complete response (pCR) at the time of surgery in each of the three arms. In the intent-to-treat population, we observed similar pCR rates between T (47%, 95% confidence interval [CI] 30–65%) and TL (52%, 95% CI 38–65%), and a lower pCR rate with L (25%, 95% CI 13–43%). In the T arm, 100% of participants completed all protocol-specified treatment prior to surgery, as compared to 69% in the L arm and 74% in the TL arm. Tumor or tumor bed tissue was collected whenever possible pre-treatment (N = 110), after one cycle of HER2-targeted therapy alone (N = 89), and at time of surgery (N = 59). Higher-level amplification of HER2 and hormone receptor (HR)-negative status were associated with a higher pCR rate. Large shifts in the tumor, immune, and stromal gene expression occurred after one cycle of HER2-targeted therapy. In contrast to pCR rates, the L-containing arms exhibited greater proliferation reduction than T at this timepoint. Immune expression signatures increased in all arms after one cycle of HER2-targeted therapy, decreasing again by the time of surgery. Our results inform approaches to early assessment of sensitivity to anti-HER2 therapy and shed light on the role of the immune microenvironment in response to HER2-targeted agents.


2019 ◽  
Vol 12 (8) ◽  
pp. 815-824 ◽  
Author(s):  
Anne Julienne Genuino ◽  
Usa Chaikledkaew ◽  
Due Ong The ◽  
Thanyanan Reungwetwattana ◽  
Ammarin Thakkinstian

2008 ◽  
Vol 6 (2) ◽  
pp. 93-104 ◽  
Author(s):  
Gabriella Mariani ◽  
Angelica Fasolo ◽  
Elena De Benedictis ◽  
Luca Gianni

2017 ◽  
Vol 35 (24) ◽  
pp. 2838-2847 ◽  
Author(s):  
Ian Krop ◽  
Nofisat Ismaila ◽  
Fabrice Andre ◽  
Robert C. Bast ◽  
William Barlow ◽  
...  

Purpose This focused update addresses the use of MammaPrint (Agendia, Irvine, CA) to guide decisions on the use of adjuvant systemic therapy. Methods ASCO uses a signals approach to facilitate guideline updates. For this focused update, the publication of the phase III randomized MINDACT (Microarray in Node-Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy) study to evaluate the MammaPrint assay in 6,693 women with early-stage breast cancer provided a signal. An expert panel reviewed the results of the MINDACT study along with other published literature on the MammaPrint assay to assess for evidence of clinical utility. Recommendations If a patient has hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative, node-negative breast cancer, the MammaPrint assay may be used in those with high clinical risk to inform decisions on withholding adjuvant systemic chemotherapy due to its ability to identify a good-prognosis population with potentially limited chemotherapy benefit. Women in the low clinical risk category did not benefit from chemotherapy regardless of genomic MammaPrint risk group. Therefore, the MammaPrint assay does not have clinical utility in such patients. If a patient has hormone receptor–positive, HER2-negative, node-positive breast cancer, the MammaPrint assay may be used in patients with one to three positive nodes and a high clinical risk to inform decisions on withholding adjuvant systemic chemotherapy. However, such patients should be informed that a benefit from chemotherapy cannot be excluded, particularly in patients with greater than one involved lymph node. The clinician should not use the MammaPrint assay to guide decisions on adjuvant systemic therapy in patients with hormone receptor–positive, HER2-negative, node-positive breast cancer at low clinical risk, nor any patient with HER2-positive or triple-negative breast cancer, because of the lack of definitive data in these populations. Additional information can be found at www.asco.org/breast-cancer-guidelines and www.asco.org/guidelineswiki .


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