Tumor size and overall survival in a cohort of young (≤40 years), nodenegative, systemically untreated breast cancer patients; by the PARADIGM study group

Abstract Background In the 1990s, the use of adjuvant systemic therapy was based on nodal involvement but not on tumor size, as was recommended in the Dutch breast cancer guidelines. Tumor size is an important prognostic variable in breast cancer, although this may not hold true for all molecular subtypes or patient ages. Here, we studied the prognostic value of tumor size for young (≤40 years at diagnosis), systemically untreated, node-negative (N0), breast cancer patients, and assessed whether for any given T-stage survival exceeds 90% at 20 years. Methods All female, breast cancer patients, ≤40 years at time of diagnosis (between 1989 and 2000), were selected from the Netherlands Cancer Registry. All lymph node-positive and systemically treated patients were excluded, resulting in a cohort of 2302 women. Clinico-pathological and follow-up data were collected from national databases, patient records, and the original pathology reports. Multivariate cox regression for overall survival was performed using T-stage (TNM 8.0), molecular subtype, and tumor grade (according to Nottingham Histologic Score) as covariates. Results Survival rates at 20-years are shown in Table. Median follow-up was 17 years. Only 1% had a T3 tumor and these patients were excluded from analysis. The 20-yr OS for the 96 (4%) T1a tumors was 81% (not shown). Women with T2 tumors had a significantly lower OS compared to women with T1a (HR 1.9 P = 0.024), T1b (HR 1.7 P = > 0.001) and T1c tumors (HR 1.31 P = 0.002), adjusted for tumor grade and molecular subtype. No OS data is shown for subgroups with less than 35 patients. Table . 179PD Overall survival (OS; %) at 20 years by T-stage, molecular subtype and tumor grade (Gr) T1b T1c T2 All n OS n OS n OS n OS 359 73 1114 69 611 60 2302 68 ER+HER2- Gr 1 + 2 Gr 3 172 82 464 77 165 56 973 73 43 68 130 55 83 49 269 54 All 79 72 55 69 ER-HER2- Gr 1 + 2 Gr 3 6 - 31 - 27 - 70 65 31 - 205 73 158 66 417 68 All 61 71 63 68 HER2+ Gr 1 + 2 Gr 3 31 - 74 54 36 54 159 57 22 - 81 53 54 61 169 56 All 70 54 57 58 Conclusions T-stage is associated with OS in this patient group. At 20 years follow-up, we found no T-stage with OS rates >90% in N0, systemically untreated patients, meaning that patients regardless of T-stage may benefit from some form of systemic treatment. Legal entity responsible for the study The PARADIGM study group. Funding The Netherlands Organization for Health Research and Development (ZonMW); A Sister’s Hope; De Vrienden van UMC Utrecht. Disclosure S.C. Linn: Research grant / Funding (self): Amgen; Research grant / Funding (self), unrestricted research grant SUBITO study (NCT02810743): Eurocept-pharmaceuticals; Research grant / Funding (institution), research grant NCT02810743 & olaparib;fulvestrant NCT00738777;advisory board olaparib breast cancer: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Roche; Research grant / Funding (institution), unrestricted research grant for NCT02285179 and study drug (taselisib): Genentech; Advisory / Consultancy, Member of the Scientific Advisory Board of Cergentis (unpaid): Cergentis; Advisory / Consultancy, scientific advisory board for Watson for Oncology (paid to institution): IBM; Research grant / Funding (institution), unrestricted research grant and study drug NCT03283384; research support biomarker study NCT02109913: Novartis; Advisory / Consultancy, Research grant / Funding (institution), scientific advisory board palbociclib; TEAM 2b through unrestricted research grant from Pfizer: Pfizer; Research grant / Funding (institution), Unrestricted research grant paid to institution for ABC study and study drug: Tesaro; Honoraria (institution), Fee for teaching paid to institution: Bayer. All other authors have declared no conflicts of interest.