Top

Breast Cancer Research and Treatment

Published in:

01-10-2019 | Breast Cancer | Epidemiology

Quantifying the relationship between age at diagnosis and breast cancer-specific mortality

Authors: Helen M. Johnson, William Irish, Mahvish Muzaffar, Nasreen A. Vohra, Jan H. Wong

Published in: Breast Cancer Research and Treatment | Issue 3/2019

Abstract

Purpose

The relationship between age at diagnosis and breast cancer-specific mortality (BCSM) is unclear. The aim of this study was to examine the nature of this relationship using rigorous statistical methodology.

Methods

A historical cohort study of adult women with invasive breast cancer in the SEER database from 2000 to 2015 was conducted. Multivariable Cox’s cause-specific hazards model was used to evaluate the association of age at diagnosis with risk of BCSM. Functional relationship of age was assessed using cumulative sums of Martingale residuals and the Kolmogorov-type supremum test.

Results

A total of 206,332 women were eligible for study. Mean age at diagnosis was 59.7 ± 13.8 years. Median follow-up was 80 months. During the study period, 21,771 women (10.6%) died from breast cancer and 18,566 (9.0%) died from other causes. Cumulative incidence of BCSM at 120 months post-diagnosis was 14.4% (95% CI 14.2–14.6%). Age was found to be quadratically related to the risk of BCSM (p < 0.001), with a nadir at 45 years of age. The final Cox model suggests that a 30-year-old woman has approximately the same adjusted BCSM risk (HR 1.187, 95% CI 1.187–1.188) as a 60-year-old woman (HR 1.174, 95% CI 1.174–1.175).

Conclusions

Women diagnosed with breast cancer at the extremes of age suffer disproportionate rates of cancer-specific mortality. The relationship between age at diagnosis and adjusted risk of BCSM is complex, consistent with a quadratic function. With the growing appreciation for breast cancer as a heterogeneous disease, it is essential to accurately address age as a prognostic risk factor in predictive models.

Available only for authorised users

Allemani C, Weir HK, Carreira H, Harewood R, Spika D, Wang XS, Bannon F, Ahn JV, Johnson CJ, Bonaventure A, Marcos-Gragera R, Stiller C, Azevedo e Silva G, Chen WQ, Ogunbiyi OJ, Rachet B, Soeberg MJ, You H, Matsuda T, Bielska-Lasota M, Storm H, Tucker TC, Coleman MP, Group CW (2015) Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet 385(9972):977–1010. https://doi.org/10.1016/S0140-6736(14)62038-9 CrossRef

Jemal A, Ward EM, Johnson CJ, Cronin KA, Ma J, Ryerson B, Mariotto A, Lake AJ, Wilson R, Sherman RL, Anderson RN, Henley SJ, Kohler BA, Penberthy L, Feuer EJ, Weir HK (2017) Annual Report to the Nation on the Status of Cancer, 1975–2014, Featuring Survival. J Natl Cancer Inst. https://doi.org/10.1093/jnci/djx030 CrossRefPubMedPubMedCentral

Berry DA, Cronin KA, Plevritis SK, Fryback DG, Clarke L, Zelen M, Mandelblatt JS, Yakovlev AY, Habbema JD, Feuer EJ, Collaborators CIaSMNC (2005) Effect of screening and adjuvant therapy on mortality from breast cancer. N Engl J Med 353(17):1784–1792. https://doi.org/10.1056/NEJMoa050518 CrossRefPubMed

Siegel RL, Miller KD (2019) Jemal A (2019) Cancer statistics. CA Cancer J Clin 69(1):7–34. https://doi.org/10.3322/caac.21551 CrossRefPubMed

Kohler BA, Sherman RL, Howlader N, Jemal A, Ryerson AB, Henry KA, Boscoe FP, Cronin KA, Lake A, Noone AM, Henley SJ, Eheman CR, Anderson RN, Penberthy L (2015) Annual Report to the Nation on the Status of Cancer, 1975–2011, Featuring incidence of breast cancer subtypes by race/ethnicity, poverty, and state. J Natl Cancer Inst 107(6):48. https://doi.org/10.1093/jnci/djv048 CrossRef

Verdial FC, Etzioni R, Duggan C, Anderson BO (2017) Demographic changes in breast cancer incidence, stage at diagnosis and age associated with population-based mammographic screening. J Surg Oncol 115(5):517–522. https://doi.org/10.1002/jso.24579 CrossRefPubMedPubMedCentral

Zhang X, Yang J, Cai H, Ye Y (2018) Young age is an independent adverse prognostic factor in early stage breast cancer: a population-based study. Cancer Manag Res 10:4005–4018. https://doi.org/10.2147/CMAR.S167363 CrossRefPubMedPubMedCentral

Gnerlich JL, Deshpande AD, Jeffe DB, Sweet A, White N, Margenthaler JA (2009) Elevated breast cancer mortality in women younger than age 40 years compared with older women is attributed to poorer survival in early-stage disease. J Am Coll Surg 208(3):341–347. https://doi.org/10.1016/j.jamcollsurg.2008.12.001 CrossRefPubMedPubMedCentral

de la Rochefordiere A, Asselain B, Campana F, Scholl SM, Fenton J, Vilcoq JR, Durand JC, Pouillart P, Magdelenat H, Fourquet A (1993) Age as prognostic factor in premenopausal breast carcinoma. Lancet 341(8852):1039–1043CrossRefPubMed

10.

Jayasinghe UW, Taylor R, Boyages J (2005) Is age at diagnosis an independent prognostic factor for survival following breast cancer? ANZ J Surg 75(9):762–767. https://doi.org/10.1111/j.1445-2197.2005.03515.x CrossRefPubMed

11.

Balabram D, Turra CM, Gobbi H (2015) Association between age and survival in a cohort of Brazilian patients with operable breast cancer. Cad Saude Publica 31(8):1732–1742. https://doi.org/10.1590/0102-311X00114214 CrossRefPubMed

12.

Roder DM, de Silva P, Zorbas HM, Kollias J, Malycha PL, Pyke CM, Campbell ID (2012) Age effects on survival from early breast cancer in clinical settings in Australia. ANZ J Surg 82(7–8):524–528. https://doi.org/10.1111/j.1445-2197.2012.06114.x CrossRefPubMed

13.

Brandt J, Garne JP, Tengrup I, Manjer J (2015) Age at diagnosis in relation to survival following breast cancer: a cohort study. World J Surg Oncol 13:33. https://doi.org/10.1186/s12957-014-0429-x CrossRefPubMedPubMedCentral

14.

Chen HL, Zhou MQ, Tian W, Meng KX, He HF (2016) Effect of age on breast cancer patient prognoses: a population-based study using the SEER 18 database. PLoS ONE 11(10):e0165409. https://doi.org/10.1371/journal.pone.0165409 CrossRefPubMedPubMedCentral

15.

Schonberg MA, Marcantonio ER, Li D, Silliman RA, Ngo L, McCarthy EP (2010) Breast cancer among the oldest old: tumor characteristics, treatment choices, and survival. J Clin Oncol 28(12):2038–2045. https://doi.org/10.1200/JCO.2009.25.9796 CrossRefPubMedPubMedCentral

16.

Lodi M, Scheer L, Reix N, Heitz D, Carin AJ, Thiébaut N, Neuberger K, Tomasetto C, Mathelin C (2017) Breast cancer in elderly women and altered clinico-pathological characteristics: a systematic review. Breast Cancer Res Treat 166(3):657–668. https://doi.org/10.1007/s10549-017-4448-5 CrossRefPubMed

17.

National Cancer Institute. Overview of the SEER Program. https://seer.cancer.gov/about/overview.html. Accessed 21 Mar 2019

18.

Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat Database: Incidence—SEER 18 Regs Custom Data (with additional treatment fields), Nov 2017 Sub (1973-2015 varying)—Linked to County Attributes—Total U.S., 1969-2016 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, released April 2018, based on the November 2017 submission. Accessed 24 August 2018

19.

National Cancer Institute. Breast Subtype (2010 +). https://seer.cancer.gov/seerstat/databases/ssf/breast-subtype.html. Accessed 21, Mar 2019

20.

Lin DY, Wei LJ, Ying Z (1993) Checking the cox model with cumulative sums of martingale-based residuals. Biometrika 80(3):557–572. https://doi.org/10.2307/2337177 CrossRef

21.

Rosenberg J, Chia YL, Plevritis S (2005) The effect of age, race, tumor size, tumor grade, and disease stage on invasive ductal breast cancer survival in the US SEER database. Breast Cancer Res Treat 89(1):47–54. https://doi.org/10.1007/s10549-004-1470-1 CrossRefPubMed

22.

Tai P, Cserni G, Van De Steene J, Vlastos G, Voordeckers M, Royce M, Lee SJ, Vinh-Hung V, Storme G (2005) Modeling the effect of age in T1-2 breast cancer using the SEER database. BMC Cancer 5:130. https://doi.org/10.1186/1471-2407-5-130 CrossRefPubMedPubMedCentral

23.

Hortobagyi GNCJ, Edge SB et al (2018) Breast. In: Amin MB, Edge S, Greene F et al (eds) AJCC Cancer Staging Manual, 8th edn. Springer, New York

24.

Fredholm H, Eaker S, Frisell J, Holmberg L, Fredriksson I, Lindman H (2009) Breast cancer in young women: poor survival despite intensive treatment. PLoS ONE 4(11):e7695. https://doi.org/10.1371/journal.pone.0007695 CrossRefPubMedPubMedCentral

25.

Klauber-DeMore N (2005) Tumor biology of breast cancer in young women. Breast Dis 23:9–15CrossRefPubMed

26.

Noone AM, Lund JL, Mariotto A, Cronin K, McNeel T, Deapen D, Warren JL (2016) Comparison of SEER Treatment data with medicare claims. Med Care 54(9):e55–64. https://doi.org/10.1097/MLR.0000000000000073 CrossRefPubMedPubMedCentral

27.

Anders CK, Hsu DS, Broadwater G, Acharya CR, Foekens JA, Zhang Y, Wang Y, Marcom PK, Marks JR, Febbo PG, Nevins JR, Potti A, Blackwell KL (2008) Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression. J Clin Oncol 26(20):3324–3330. https://doi.org/10.1200/JCO.2007.14.2471 CrossRefPubMed

28.

Wang MX, Ren JT, Tang LY, Ren ZF (2018) Molecular features in young vs elderly breast cancer patients and the impacts on survival disparities by age at diagnosis. Cancer Med 1:1–10. https://doi.org/10.1002/cam4.1544 CrossRef

29.

Borges VF, Schedin PJ (2012) Pregnancy-associated breast cancer: an entity needing refinement of the definition. Cancer 118(13):3226–3228. https://doi.org/10.1002/cncr.26643 CrossRefPubMed

30.

Callihan EB, Gao D, Jindal S, Lyons TR, Manthey E, Edgerton S, Urquhart A, Schedin P, Borges VF (2013) Postpartum diagnosis demonstrates a high risk for metastasis and merits an expanded definition of pregnancy-associated breast cancer. Breast Cancer Res Treat 138(2):549–559. https://doi.org/10.1007/s10549-013-2437-x CrossRefPubMedPubMedCentral

31.

Johansson AL, Andersson TM, Hsieh CC, Cnattingius S, Lambe M (2011) Increased mortality in women with breast cancer detected during pregnancy and different periods postpartum. Cancer Epidemiol Biomarkers Prev 20(9):1865–1872. https://doi.org/10.1158/1055-9965.EPI-11-0515 CrossRefPubMed

32.

Varghese F, Wong J (2018) Breast Cancer in the Elderly. Surg Clin North Am 98(4):819–833. https://doi.org/10.1016/j.suc.2018.04.002 CrossRefPubMed

33.

Hughes KS, Schnaper LA, Bellon JR, Cirrincione CT, Berry DA, McCormick B, Muss HB, Smith BL, Hudis CA, Winer EP, Wood WC (2013) Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343. J Clin Oncol 31(19):2382–2387. https://doi.org/10.1200/JCO.2012.45.2615 CrossRefPubMedPubMedCentral

34.

Kunkler IH, Williams LJ, Jack WJ, Cameron DA, Dixon JM, Investigators PI (2015) Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial. Lancet Oncol 16(3):266–273. https://doi.org/10.1016/S1470-2045(14)71221-5 CrossRefPubMed

35.

Society of Surgical Oncology. Choosing Wisely: Five Things that Patients and Physicians Should Question. (2016). http://www.choosingwisely.org/societies/society-of-surgical-oncology/. Accessed 7 Apr 2019

36.

Mamtani A, Gonzalez JJ, Neo DT, Friedman RS, Recht A, Hacker MR, Sharma R (2018) Treatment strategies in octogenarians with early-stage high-risk breast cancer. Ann Surg Oncol 25(6):1495–1501. https://doi.org/10.1245/s10434-018-6350-8 CrossRefPubMedPubMedCentral

37.

Gajdos C, Tartter PI, Bleiweiss IJ, Lopchinsky RA, Bernstein JL (2001) The consequence of undertreating breast cancer in the elderly. J Am Coll Surg 192(6):698–707CrossRefPubMed

38.

Yood MU, Owusu C, Buist DS, Geiger AM, Field TS, Thwin SS, Lash TL, Prout MN, Wei F, Quinn VP, Frost FJ, Silliman RA (2008) Mortality impact of less-than-standard therapy in older breast cancer patients. J Am Coll Surg 206(1):66–75. https://doi.org/10.1016/j.jamcollsurg.2007.07.015 CrossRefPubMed

39.

Bouchardy C, Rapiti E, Fioretta G, Laissue P, Neyroud-Caspar I, Schäfer P, Kurtz J, Sappino AP, Vlastos G (2003) Undertreatment strongly decreases prognosis of breast cancer in elderly women. J Clin Oncol 21(19):3580–3587. https://doi.org/10.1200/JCO.2003.02.046 CrossRefPubMed

40.

Rao VS, Jameel JK, Mahapatra TK, McManus PL, Fox JN, Drew PJ (2007) Surgery is associated with lower morbidity and longer survival in elderly breast cancer patients over 80. Breast J 13(4):368–373. https://doi.org/10.1111/j.1524-4741.2007.00444.x CrossRefPubMed

41.

Tamirisa N, Thomas SM, Fayanju OM, Greenup RA, Rosenberger LH, Hyslop T, Hwang ES, Plichta JK (2018) Axillary nodal evaluation in elderly breast cancer patients: potential effects on treatment decisions and survival. Ann Surg Oncol 25(10):2890–2898. https://doi.org/10.1245/s10434-018-6595-2 CrossRefPubMedPubMedCentral

42.

Azim HA, Nguyen B, Brohée S, Zoppoli G, Sotiriou C (2015) Genomic aberrations in young and elderly breast cancer patients. BMC Med 13:266. https://doi.org/10.1186/s12916-015-0504-3 CrossRefPubMedPubMedCentral

43.

Adami HO, Malker B, Holmberg L, Persson I, Stone B (1986) The relation between survival and age at diagnosis in breast cancer. N Engl J Med 315(9):559–563. https://doi.org/10.1056/NEJM198608283150906 CrossRefPubMed

44.

Cluze C, Colonna M, Remontet L, Poncet F, Sellier E, Seigneurin A, Delafosse P, Bossard N (2009) Analysis of the effect of age on the prognosis of breast cancer. Breast Cancer Res Treat 117(1):121–129. https://doi.org/10.1007/s10549-008-0222-z CrossRefPubMed

45.

Forsare C, Bak M, Falck AK, Grabau D, Killander F, Malmström P, Rydén L, Stål O, Sundqvist M, Bendahl PO, Fernö M (2018) Non-linear transformations of age at diagnosis, tumor size, and number of positive lymph nodes in prediction of clinical outcome in breast cancer. BMC Cancer 18(1):1226. https://doi.org/10.1186/s12885-018-5123-x CrossRefPubMedPubMedCentral

46.

Haddad RI, Nasr C, Bischoff L, Busaidy NL, Byrd D, Callender G, Dickson P, Duh QY, Ehya H, Goldner W, Haymart M, Hoh C, Hunt JP, Iagaru A, Kandeel F, Kopp P, Lamonica DM, McIver B, Raeburn CD, Ridge JA, Ringel MD, Scheri RP, Shah JP, Sippel R, Smallridge RC, Sturgeon C, Wang TN, Wirth LJ, Wong RJ, Johnson-Chilla A, Hoffmann KG, Gurski LA (2018) NCCN guidelines insights: Thyroid carcinoma, Version 2.2018. J Natl Compr Canc Netw 16(12):1429–1440. https://doi.org/10.6004/jnccn.2018.0089 CrossRefPubMed

47.

Wishart GC, Bajdik CD, Dicks E, Provenzano E, Schmidt MK, Sherman M, Greenberg DC, Green AR, Gelmon KA, Kosma VM, Olson JE, Beckmann MW, Winqvist R, Cross SS, Severi G, Huntsman D, Pylkäs K, Ellis I, Nielsen TO, Giles G, Blomqvist C, Fasching PA, Couch FJ, Rakha E, Foulkes WD, Blows FM, Bégin LR, van’t Veer LJ, Southey M, Nevanlinna H, Mannermaa A, Cox A, Cheang M, Baglietto L, Caldas C, Garcia-Closas M, Pharoah PD (2012) PREDICT Plus: development and validation of a prognostic model for early breast cancer that includes HER2. Br J Cancer 107(5):800–807. https://doi.org/10.1038/bjc.2012.338 CrossRefPubMedPubMedCentral

48.

Olivotto IA, Bajdik CD, Ravdin PM, Speers CH, Coldman AJ, Norris BD, Davis GJ, Chia SK, Gelmon KA (2005) Population-based validation of the prognostic model ADJUVANT! for early breast cancer. J Clin Oncol 23(12):2716–2725. https://doi.org/10.1200/JCO.2005.06.178 CrossRefPubMed

Title: Quantifying the relationship between age at diagnosis and breast cancer-specific mortality
Authors: Helen M. Johnson
William Irish
Mahvish Muzaffar
Nasreen A. Vohra
Jan H. Wong
Publication date: 01-10-2019
Publisher: Springer US
Keywords: Breast Cancer
Breast Cancer
Published in: Breast Cancer Research and Treatment / Issue 3/2019
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-019-05353-2

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 3/2019

The relationship between ring-type dedicated breast PET and immune microenvironment in early breast cancer

Social determinants of breast cancer risk, stage, and survival

A generalizable relationship between mortality and time-to-death among breast cancer patients can be explained by tumour dormancy

Talking about risk in the context of genomic tests (TARGET): development and evaluation of an educational program for clinicians

Mode of detection and breast cancer mortality by follow-up time and tumor characteristics among screened women in Cancer Prevention Study-II

The prognostic significance of preoperative tumor marker (CEA, CA15-3) elevation in breast cancer patients: data from the Korean Breast Cancer Society Registry

Keynote webinar | Spotlight on antibody–drug conjugates in cancer