Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2021 May 28;5(4):pkab054.
doi: 10.1093/jncics/pkab054. eCollection 2021 Aug.

MAF Amplification and Adjuvant Clodronate Outcomes in Early-Stage Breast Cancer in NSABP B-34 and Potential Impact on Clinical Practice

Alexander H G Paterson  1 , Peter C Lucas  1 , Stewart J Anderson  1 , Eleftherios P Mamounas  1 , Adam Brufsky  1 , Luis Baez-Diaz  1 , Karen M King  1 , Thomas Lad  1 , André Robidoux  1 , Melanie Finnigan  1 , Miguel Sampayo  2 , Juan Carlos Tercero  3 , Joël Jean Mairet  3 , Antonio C Wolff  1 , Louis Fehrenbacher  1 , Norman Wolmark  1 , Roger R Gomis  4
Affiliations
Randomized Controlled Trial

MAF Amplification and Adjuvant Clodronate Outcomes in Early-Stage Breast Cancer in NSABP B-34 and Potential Impact on Clinical Practice

Alexander H G Paterson et al. JNCI Cancer Spectr. .

Abstract

Background: The Adjuvant Zoledronic Acid (ZA) study in early breast cancer (AZURE) showed correlation between a nonamplified MAF gene in the primary tumor and benefit from adjuvant ZA. Adverse ZA outcomes occurred in MAF-amplified patients. NSABP B-34 is a validation study.

Methods: A retrospective analysis of MAF gene status in NSABP B-34 was performed. Eligible patients were randomly assigned to standard adjuvant systemic treatment plus 3 years oral clodronate (1600 mg/daily) or placebo. Tumors were tested for MAF gene amplification and analyzed for their relationship to clodronate for disease-free survival (DFS) and overall survival (OS) in MAF nonamplified patients. All statistical tests were 2-sided .

Results: MAF status was assessed in 2533 available primary tumor samples from 3311 patients. Of these, 37 withdrew consent; in 77 samples, no tumor was found; 536 assays did not meet quality standards, leaving 1883 (77.8%) evaluable for MAF assay by fluorescence in situ hybridization (947 from placebo and 936 from clodronate arms). At 5 years, in MAF nonamplified patients receiving clodronate, DFS improved by 30% (hazard ratio = 0.70, 95% confidence interval = 0.51 to 0.94; P = .02). OS improved at 5 years (hazard ratio = 0.59, 95% confidence interval = 0.37 to 0.93; P = .02) remaining statistically significant for clodronate throughout study follow-up. Conversely, adjuvant clodronate in women with MAF-amplified tumors was not associated with benefit but rather possible harm in some subgroups. Association between MAF status and menopausal status was not seen.

Conclusions: Nonamplified MAF showed statistically significant benefits (DFS and OS) with oral clodronate, supporting validation of the AZURE study.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Schematic representation depicting MAF test analyses on the NSABP B-34 patient population. The MAF status distribution according to patient subgroups is reported. H&E = hematoxilyin and eosin.
Figure 2.
Figure 2.
Disease-free survival (A) and percentage who died (B) by treatment group in MAF-nonamplified patients at 5-year follow-up from Cox multivariable model adjusted for differences in age, nodal status, presence of estrogen and progesterone, histological grade, and pathological tumor size. All statistical tests are 2-sided. CI = confidence interval; CLO = Clodronate; HR = hazard ratio .
Figure 3.
Figure 3.
Schematic representation depicting adjuvant bisphosphonates recommended treatment algorithm based on MAF test .
See this image and copyright information in PMC

References

    1. Coleman RE, Collinson M, Gregory W, et al.Benefits and risks of adjuvant treatment with zoledronic acid in stage II/III breast cancer. 10 years follow-up of the AZURE randomized clinical trial (BIG 01/04). J Bone Oncol. 2018;13:123–135. - PMC - PubMed
    1. Paterson AH, Anderson SJ, Lembersky BC, et al.Oral clodronate for adjuvant treatment of operable breast cancer (National Surgical Adjuvant Breast and Bowel Project protocol B-34): a multicentre, placebo-controlled, randomised trial. Lancet Oncol. 2012;13(7):734–742. - PMC - PubMed
    1. Early Breast Cancer Trials Collaborative Group. Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomized trials. Lancet. 2015;386(10001):1353–1361. - PubMed
    1. Hadji P, Coleman RE, Wilson C, et al.Adjuvant bisphosphonates in early breast cancer: Consensus guidance for clinical practice from a European Panel. Ann Oncol. 2016;27(3):379–390. - PubMed
    1. Dhesy-Thind S, Fletcher GG, Blanchette PS, et al.Use of adjuvant bisphosphonates and other bone-modifying agents in breast cancer: a cancer care Ontario and American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2017;35(18):2062–2081. - PubMed

Publication types

MeSH terms

LinkOut - more resources