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Effects of Germline Pathogenic Variants, Cancer Subtypes, Tumor-related Characteristics, and Pregnancy-associated Diagnosis on Outcomes

      Abstract

      Background

      Although breast cancer (BC) is uncommon in women age ≤ 35 years, women in this age group may have more aggressive cancer subtypes and high-risk pathogenic variants (HRPVs). Higher recurrence and mortality rates in young patients may be related to differences in tumor biology, pathologic mutation status, or treatment. The purpose of this study was to evaluate germline mutation status and other factors that affect recurrence-free survival (RFS) and overall survival (OS) in young women with BC.

      Materials and Methods

      This was a retrospective study of women diagnosed with BC at age ≤ 35 years at Allina Health System from 2000 through 2017 (n = 306). Information was collected on germline mutation status, tumor characteristics (grade, hormone receptor, and human epidermal growth factor receptor 2), molecular subtype, pregnancy-associated cancers, and treatment. Survival analyses using Kaplan-Meier curves were conducted for RFS and OS.

      Results

      With mean follow-up of 6.5 years, OS was 87.0% for invasive cancers, RFS was 84.7%; 69% obtained genetic testing, and 26.9% had HRPVs. There were no differences in RFS or OS between patients with HRPV versus unknown/low/moderate risk variants. Recurrence analysis showed increased recurrence rates in luminal B-like cancers followed by triple negative and human epidermal growth factor receptor 2-positive cancers (P = .041). Pregnancy-associated BC diagnoses, angiolymphatic invasion, and tumor stage were associated with reduced OS. In spite of young age at diagnosis, nearly one-third of patients did not receive germline genetic testing.

      Conclusions

      Similar survival patterns were found between women with HRPV versus no known mutations. Luminal B-like subtype, pregnancy-associated BC, angiolymphatic invasion, and cancer stage were associated with reduced OS.

      Keywords

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      References

        • Chen H.L.
        • Zhou M.Q.
        • Tian W.
        • Meng K.X.
        • He H.F.
        Effect of age on breast cancer patient prognoses: a population-based study using the SEER 18 database.
        PLoS One. 2016; 11: e0165409
        • DeCamargo Cancela M.
        • Comber H.
        • Sharp L.
        HR+/Her2- breast cancer in pre-menopausal women: the impact of younger age on clinical characteristics at diagnosis, disease management and survival.
        Cancer Epidemiol. 2016; 45: 162-168
        • Radecka B.
        • Litwiniuk M.
        Breast cancer in young women.
        Ginekol Pol. 2016; 87: 659-663
        • Sabiani L.
        • Houvenaeghel G.
        • Heinemann M.
        • et al.
        Breast cancer in young women: pathologic features and molecular phenotype.
        Breast. 2016; 29: 109-116
        • Liukkonen S.
        • Leidenius M.
        • Saarto T.
        • Sjöström-Mattson J.
        Breast cancer in very young women.
        Eur J Surg Oncol. 2011; 37: 1030-1037
        • Zimmer A.S.
        • Zhu K.
        • Steeg P.
        • et al.
        Analysis of breast cancer in young women in the Department of Defense (DOD) database.
        Breast Cancer Res Treat. 2018; 168: 501-511
        • Brandt J.
        • Garne J.P.
        • Tengrup K.
        • Manjer J.
        Age at diagnosis in relation to survival following breast cancer: a cohort study.
        World J Surg Oncol. 2015; 13: 33
        • Tjokrowidjaja A.
        • Lee C.K.
        • Houssami N.
        • Lord S.
        Metastatic breast cancer in young women: a population-based cohort study to describe risk and prognosis.
        Intern Med J. 2014; 44: 764-770
        • Martinez-Ramos D.
        • Escrig J.
        • Torrella A.
        • Hoashi J.S.
        • Alcalde M.
        • Salvador J.L.
        Risk of recurrence of non-metastatic breast cancer in women under 40 years: a population-registry cancer study in a European country.
        Breast J. 2012; 18: 118-123
      1. National Comprehensive Cancer Network. Available at: NCCN Clinical Practice Guidelines in Oncology. Genetic/familial high-risk assessment: breast and ovarian. V3.2019–January 18. Accessed August 6, 2019.

        • Kehl K.L.
        • Shen C.
        • Litton J.K.
        • Arun B.
        • Giordano S.H.
        Rates of BRCA1/2 mutation testing among young survivors of breast cancer.
        Breast Cancer Res Treat. 2016; 155: 165-173
        • Rummel S.K.
        • Lovejoy L.
        • Shriver C.D.
        • Ellsworth R.E.
        Contribution of germline mutations in cancer predisposition genes to tumor etiology in young women diagnosed with invasive breast cancer.
        Breast Cancer Res Treat. 2017; 164: 593-601
        • Menes T.S.
        • Terry M.B.
        • Goldgar D.
        • et al.
        Second primary breast cancer in BRCA1 and BRCA2 mutation carriers: 10-year cumulative incidence in the Breast Cancer Family Registry.
        Breast Cancer Res Treat. 2015; 151: 653-660
        • Donovan C.A.
        • Bao J.
        • Gangi A.
        • et al.
        Bilateral mastectomy as overtreatment for breast cancer in women age forty years and younger with unilateral operable invasive breast cancer.
        Ann Surg Oncol. 2017; 24: 2168-2173
        • Quan M.L.
        • Paszat L.F.
        • Fernandes K.A.
        • et al.
        The effect of surgery type on survival and recurrence in very young women with breast cancer.
        J Surg Oncol. 2017; 115: 122-130
        • Ribnikar D.
        • Ribeiro J.M.
        • Pinto D.
        • et al.
        Breast cancer under age 40: a different approach.
        Curr Treat Options Oncol. 2015; 16: 16
        • Frandsen J.
        • Ly D.
        • Cannon G.
        • et al.
        In the modern treatment era, is breast conservation equivalent to mastectomy in women younger than 40 years of age? A multi-institutional study.
        Int J Radiat Oncol Biol Phys. 2015; 93: 1096-1103
        • Maishman T.
        • Cutress R.I.
        • Hernandez A.
        • et al.
        Local recurrence and breast oncological surgery in young women with breast cancer: the POSH observational cohort study.
        Ann Surg. 2016; 266: 165-172
        • NCCN Clinical Practice Guidelines in Oncology
        Genetic/familial high risk assessment: breast, ovarian, and pancreatic. Version 1.2020 – Dec 4, 2019.
        (Available at:)
        • Partridge A.H.
        • Hughes M.E.
        • Warner E.T.
        • et al.
        Subtype-dependent relationship between young age at diagnosis and breast cancer survival.
        J Clin Oncol. 2016; 34: 3308-3314
        • Fredholm H.
        • Magnusson K.
        • Lindstrom L.S.
        • et al.
        Breast cancer in young women and prognosis: how important are proliferation markers?.
        Eur J Cancer. 2017; 84: 278-289
        • Mariotto A.B.
        • Noone A.M.
        • Howlader N.
        • et al.
        Cancer survival: an overview of measures, uses, and interpretation.
        J Natl Cancer Inst Monogr. 2014; 49: 145-186
        • Schmidt M.K.
        • van den Broek A.J.
        • Tollenaar R.A.
        • et al.
        Breast cancer survival of BRCA1/BRCA2 mutation carriers in a hospital-based cohort of young women.
        J Natl Cancer Inst. 2017; 109
        • Copson E.R.
        • Maishman T.C.
        • Tapper W.J.
        • et al.
        Germline BRCA mutation and outcome in young-onset breast cancer (POSH): a prospective cohort study.
        Lancet Oncol. 2018; 19: 169-180
        • Ha S.M.
        • Chae E.Y.
        • Cha J.H.
        • Kim H.H.
        • Shin H.J.
        • Choi W.J.
        Association of BRCA mutation types, imaging features, and pathologic findings in patients with breast cancer with BRCA1 and BRCA2 mutations.
        AJR Am J Roentgenol. 2017; 209: 920-928
        • Azim Jr., H.A.
        • Santoro L.
        • Russell-Edu W.
        • Pentheroudakis G.
        • Pavlidis N.
        • Paccatori F.A.
        Prognosis of pregnancy-associated breast cancer: a meta-analysis of 30 studies.
        Cancer Treat Rev. 2012; 38: 834-842
        • Bae S.Y.
        • Kim S.J.
        • Lee J.S.
        • et al.
        Clinical subtypes and prognosis of pregnancy-associated breast cancer: results from the Korean Breast Cancer Society Registry database.
        Breast Cancer Res Treat. 2018; 172: 113-121
        • Nichols H.B.
        • Schoemaker M.J.
        • Cai J.
        • et al.
        Breast cancer risk after recent childbirth: a pooled analysis of 15 prospective studies.
        Ann Intern Med. 2019; 170: 22-30
        • Johansson A.L.V.
        • Andersson T.M.L.
        • Hsieh C.C.
        • et al.
        Tumor characteristics and prognosis in women with pregnancy-associated breast cancer.
        Int J Cancer. 2018; 142: 1343-1354
        • Boudy A.S.
        • Naoura I.
        • Selleret L.
        • et al.
        Propensity score to evaluate prognosis in pregnancy-associated breast cancer: analysis from a French cancer network.
        Breast. 2018; 40: 10-15
        • Ploquin A.
        • Pistilli B.
        • Tresch E.
        • et al.
        5-year overall survival after early breast cancer diagnosed during pregnancy: a retrospective case-control multicenter French study.
        Eur J Cancer. 2018; 95: 30-37