Cohort studyindependent cross-checkabstract checked★ key study I-CHM-110 standard review

Leukaemia-type cancers after breast cancer treatment

Risk of marrow neoplasms after adjuvant breast cancer therapy: the national comprehensive cancer network experience.

Overview

Wolff AC et al.. J Clin Oncol 2015 · PMID 25534386 · DOI 10.1200/JCO.2013.54.6119

About 5 in 1000 treated women developed a marrow cancer within 10 years.

Does the study support the specific claim? Yes · Methodological quality: moderate

Study explained simply

What did the researchers want to find out?: Measure risk of marrow cancers after treatment
How was the study done?: Cohort of 20,063 patients
How many people, animals or samples were studied?: US academic centres
What was actually found?: Low but real risk that keeps rising after 5 years
How large was the observed effect?: 0.24% at 5 y, 0.48% at 10 y
What do the results mean in everyday life?: Rare, but a reason for follow-up
What are the study's limitations?: Few events
What does it say about Elawady's specific claim?: Supports existence of second cancers; shows they are rare
Do the results apply to Germany and Europe?: High
What can explicitly not be concluded from this study?: Cannot show harm outweighs benefit

Authors: Wolff AC et al.
Journal: J Clin Oncol
Year: 2015
Identifier: PMID 25534386 DOI 10.1200/JCO.2013.54.6119
Verification: verified – PubMed efetch 2026-10-26 (PublicationType and CommentsCorrections checked); Crossref 2026-10-26
Retracted: no
Corrections: ErratumIn J Clin Oncol 2015;33(10):1227 (PubMed); Crossref correction 10.1200/jco.2015.61.6656; no retraction
Extent checked: abstract only
Conflicts of interest and funding: NCI grants; COI not stated in abstract.

What is the risk of marrow neoplasms (MDS/AML and others) after adjuvant breast cancer therapy?

Study design: Cohort study – Retrospective multicentre cohort (NCCN database)
Population: Patients with stage I-III breast cancer at US academic centres
Country: USA
Period: Treated 1998-2007; median follow-up 5.1 years
Sample size: 20,063
Inclusion and exclusion criteria: Stage I-III breast cancer

Exposure / intervention: Adjuvant chemotherapy and/or radiotherapy
Comparator: Surgery only
Endpoints: Marrow neoplasms (myeloid and lymphoid)
Statistical methods: Cumulative incidence with competing risks; HRs; comparison with SEER

Results: 50 patients developed marrow neoplasm (42 myeloid, 8 lymphoid). HR 6.8 (1.3-36.1) after surgery plus chemotherapy and 7.6 (1.6-35.8) after all modalities vs no chemotherapy. Rates per 1000 person-years: 0.16 (surgery), 0.43 (plus radiation), 0.46 (plus chemotherapy), 0.54 (all three). Cumulative incidence 0.24% at 5 years and 0.48% at 10 years.
Absolute risks: Cumulative incidence 0.48% at 10 years
Authors' conclusion: Marrow-neoplasm risk after radiation and/or adjuvant chemotherapy was low but higher than previously described and continued beyond 5 years; individual risk must be balanced against the absolute survival benefit of chemotherapy.

Orienting tool: ROBINS-E
Type of assessment: simplified assessment (abstract only)
Full formal assessment: no
Overall risk of bias: some concerns
Rationale: Observational cohort; confounding by indication possible but direction of harm consistent with biology.

HRs have very wide CIs (few events in surgery-only group); absolute rates are the informative measure (stats/C-CHM-03.py).

Confirms therapy-related marrow cancers and quantifies them as rare (about 0.5% at 10 years).

EBCTCG 2023 (I-CHM-101) gives a similar order of magnitude (AML about 1 per 700).

Applicable to European adjuvant practice.

Real but rare harm, quantified.

Multidimensional assessment
Multidimensional assessment
Authenticity of the source	verified
Methodological quality	moderate
Risk of bias	some concerns
Precision of results	low
Directness	direct
Reproducibility	replicated
Consistency with the overall evidence	consistent
Regional transferability	high
Adequacy of the interpretation (by the archive)	not applicable

Risk beyond 10 years.