The Absolute Effect / Evidence / Breast Cancer
ACOSOG Z11102 (Alliance)
Clinical question: In selected women with two or three ipsilateral breast cancer foci, can breast-conserving therapy achieve an acceptably low 5-year local recurrence rate?
Registry: NCT01585428 · One underlying study; aliases and follow-up publications consolidated.
Design, population and eligibility
Prospective, multicentre, single-arm phase II surgical trial
270 women enrolled; 204 eligible patients underwent protocol-directed breast-conserving therapy. Median age 61 years; most had two sites and ER-positive/HER2-negative disease.
Women aged ≥40 years with two or three biopsy-proven ipsilateral breast cancer foci, at least one invasive focus, with disease amenable to lumpectomy and negative margins. The cohort was selected; inflammatory breast cancer and diffuse disease unsuitable for conservation were not represented.
Follow-up and endpoint maturity are stated with the reported efficacy results; further long-term updates are noted where applicable.
Treatment and comparator
Breast-conserving surgery with negative margins, followed by whole-breast irradiation and a boost to each lumpectomy bed. Systemic therapy was given according to tumour biology and usual clinical indications; this was not a randomized comparison of radiation or systemic regimens.
Primary and secondary endpoints
Primary endpoint: 5-year cumulative incidence of local recurrence, with a prespecified clinically acceptable threshold <8%. Secondary endpoints included regional recurrence, distant recurrence, disease-free and overall survival, and the role of preoperative MRI.
Key efficacy results
At median follow-up 66.4 months, 6 local recurrences occurred; estimated 5-year cumulative local recurrence was 3.1% (95% CI 1.3–6.4), below the prespecified 8% acceptability threshold. No regional recurrences were reported in the analysed cohort.
Exploratory MRI subgroup: 5-year local recurrence was 1.7% among 189 patients with preoperative MRI versus 22.6% among 15 without MRI (P=0.002). This small non-randomized subgroup comparison is hypothesis-generating and cannot establish an MRI treatment effect.
Source-reported outcome visualization
Five-year cumulative local recurrence.
Single-arm outcome. The 8% line is the prespecified acceptability threshold; no comparator arm or comparative NNT exists.
Absolute effect
5-year local recurrence was 3.1% (95% CI 1.3–6.4) in the eligible treated cohort. There is no randomized comparator, so absolute risk reduction and NNT are not estimable. The observed rate was 4.9 percentage points below the protocol's 8% acceptability threshold; this is not a treatment effect.
Trial-specific toxicity and treatment burden
The study does not provide a randomized comparison of surgical complications, cosmesis or radiation toxicity against mastectomy. Treatment burden includes multiple excisions where required, whole-breast RT and boosts to each tumour bed. Toxicity estimates should not be inferred from the local recurrence endpoint.
Quality of life and patient-reported outcomes
No randomized QoL comparison with mastectomy was performed. Patient-reported cosmetic and psychosocial outcomes are not sufficient to establish comparative QoL superiority.
Subgroups and applicability
Most participants had two foci and ER-positive/HER2-negative disease. MRI subgroup findings are exploratory (n=15 without MRI). Tumour biology and number of foci were not shown to predict local recurrence in this modest event set.
Current-practice context · reviewed 3 November 2026
Supports breast conservation as an option for carefully selected patients with two or three ipsilateral foci after appropriate imaging, biopsy confirmation, margin-negative excision and whole-breast irradiation with boosts. It does not establish suitability for diffuse multicentric disease or all patients with multiple lesions.
Limitations and critical interpretation
Single-arm phase II design; only 204 eligible patients received protocol-directed breast conservation and six local recurrences occurred. No randomized mastectomy comparator, no power for survival equivalence and a very small no-MRI subgroup.
Bottom line: Z11102 expands the evidence base for breast conservation in selected multiple ipsilateral breast cancer. Its 3.1% 5-year local recurrence rate is reassuring but should not be misread as randomized equivalence to mastectomy.
Primary sources and follow-up publications
Outcome values are sourced from the linked reports. Unreported values are not imputed. NNT/NNH is only stated when an explicit fixed-time absolute difference supports a defensible calculation; no NNT is derived from median survival.