. 2015 Mar; 16(4):16.
doi: 10.1007/s11864-015-0334-8.

Breast cancer under age 40: a different approach

D Ribnikar 1 J M Ribeiro  D Pinto  B Sousa  A C Pinto  E Gomes  E C Moser  M J Cardoso  F Cardoso  
  • PMID: 25796377
  •     117 References
  •     23 citations


Breast cancer (BC) under age 40 is a complex disease to manage due to the additionally fertility-related factors to be taken in consideration. More than 90% of young patients with BC are symptomatic. Women<40 years are more likely to develop BC with worse clinicopathological features and more aggressive subtype. This has been frequently associated with inferior outcomes. Recently, the prognostic significance of age<40 has been shown to differ according to the BC subtype, being associated with worst recurrence-free survival (RFS) and overall survival (OS) for luminal BC. The biology of BC<40 has also been explored through analysis of large genomic data set, and specific pathways overexpressed in these tumors have been identified which can lead to the development of targeted therapy in the future. A multidisciplinary tumor board should determine the optimal locoregional and systemic management strategies for every individual patient with BC before the start of any therapy including surgery. This applies to both early (early breast cancer (EBC)) and advanced (advanced breast cancer (ABC)) disease, before the start of any therapy. Mastectomy even in young patients confers no overall survival advantage when compared to breast-conserving treatment (BCT), followed by radiotherapy. Regarding axillary approach, indications are identical to other age groups. Young age is one of the most important risk factors for local recurrence after both breast-conserving surgery (BCS) and mastectomy, associated with a higher risk of distant metastasis and death. Radiation after BCS reduces local recurrence from 19.5 to 10.2% in BC patients 40 years and younger. The indications for and the choice of systemic treatment for invasive BC (both early and advanced disease) should not be based on age alone but driven by the biological characteristics of the individual tumor (including hormone receptor status, human epidermal growth factor receptor 2 (HER-2) status, grade, and proliferative activity), disease stage, and patient's comorbidities. Recommendations regarding the use of genomic profiles such as MammaPrint, Oncotype Dx, and Genomic grade index in young women are similar to the general BC population. Especially in the metastatic setting, patient preferences should always be taken into account, as the disease is incurable. The best strategy for these patients is the inclusion into well-designed, independent, prospective randomized clinical trials. Metastatic disease should always be biopsied whenever feasible for histological confirmation and reassessment of biology. Endocrine therapy is the preferred option for hormone receptor-positive disease (HR+ve), even in presence of visceral metastases, unless there is concern or proof of endocrine resistance or there is a need for rapid disease response and/or symptom control. Recommendations for chemotherapy (CT) should not differ from those for older patients with the same characteristics of the metastatic disease and its extent. Young age by itself should not be an indication to prescribe more intensive and combination CT regimens over the sequential use of monotherapy. Poly(ADP-ribose) polymerase inhibitors (PARP inhibitors) represent an important group of promising drugs in managing patients with breast cancer susceptibility gene (BRCA)-1- or BRCA-2-associated BC. Specific age-related side effects of systemic treatment (e.g., menopausal symptoms, change in body image, bone morbidity, cognitive function impairment, fertility damage, sexual dysfunction) and the social impact of diagnosis and treatment (job discrimination, taking care for children) should also be carefully addressed when planning systemic long-lasting therapy, such as endocrine therapy. Survivorship concerns for young women are different compared to older women, including issues of fertility, preservation, and pregnancy.

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K David Voduc, Maggie C U Cheang, +3 authors, Hagen Kennecke.
J Clin Oncol, 2010 Mar 03; 28(10). PMID: 20194857
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Ovarian function preservation with GnRH agonist in young breast cancer patients: does it impede the effect of adjuvant chemotherapy?
Jiyoung Kim, Minkook Kim, +8 authors, Seok Jin Nam.
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Breast-conserving treatment with or without radiotherapy in ductal carcinoma In Situ: 15-year recurrence rates and outcome after a recurrence, from the EORTC 10853 randomized phase III trial.
Mila Donker, Saskia Litière, +9 authors, Nina Bijker.
J Clin Oncol, 2013 Sep 18; 31(32). PMID: 24043739
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Relationship between age at diagnosis and outcome of premenopausal breast cancer: age less than 35 years is a reasonable cut-off for defining young age-onset breast cancer.
Wonshik Han, So Young Kang, Korean Breast Cancer Society.
Breast Cancer Res Treat, 2009 Apr 08; 119(1). PMID: 19350387
Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update.
Antonio C Wolff, M Elizabeth H Hammond, +19 authors, College of American Pathologists.
J Clin Oncol, 2013 Oct 09; 31(31). PMID: 24101045
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Impact of a higher radiation dose on local control and survival in breast-conserving therapy of early breast cancer: 10-year results of the randomized boost versus no boost EORTC 22881-10882 trial.
Harry Bartelink, Jean-Claude Horiot, +9 authors, Laurence Collette.
J Clin Oncol, 2007 Jun 20; 25(22). PMID: 17577015
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Long-term follow-up of a prospective policy of margin-directed radiation dose escalation in breast-conserving therapy.
Andrew C Neuschatz, Thomas DiPetrillo, +3 authors, David E Wazer.
Cancer, 2002 Dec 20; 97(1). PMID: 12491502
Commentary on "aTTom": long-term effects of continuing adjuvant Tamoxifen to 10 years.
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Chin Clin Oncol, 2015 Apr 07; 3(1). PMID: 25842085
Is mastectomy superior to breast-conserving treatment for young women?
Geneviève Coulombe, Scott Tyldesley, +6 authors, Ivo A Olivotto.
Int J Radiat Oncol Biol Phys, 2007 Feb 06; 67(5). PMID: 17275207
Variability in measuring the Ki-67 labeling index in patients with breast cancer.
Shinya Yamamoto, Takashi Chishima, +7 authors, Kentaro Sakamaki.
Clin Breast Cancer, 2014 Dec 03; 15(1). PMID: 25445422
Oncofertility: an emerging discipline in obstetrics and gynecology.
Sara Lange, David Tait, Michelle Matthews.
Obstet Gynecol Surv, 2013 Aug 08; 68(8). PMID: 23921672
Risk of ipsilateral breast cancer in BRCA1 and BRCA2 mutation carriers.
Kelly Metcalfe, Henry T Lynch, +10 authors, Steven A Narod.
Breast Cancer Res Treat, 2011 Jan 12; 127(1). PMID: 21221768
Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.
E Senkus, S Kyriakides, +5 authors, ESMO Guidelines Working Group.
Ann Oncol, 2013 Aug 24; 24 Suppl 6. PMID: 23970019
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ESO-ESMO 2nd international consensus guidelines for advanced breast cancer (ABC2).
F Cardoso, A Costa, +42 authors, European Society of Medical Oncology.
Breast, 2014 Sep 24; 23(5). PMID: 25244983
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Levonorgestrel-releasing and copper intrauterine devices and the risk of breast cancer.
Jürgen Dinger, Kristina Bardenheuer, Thai Do Minh.
Contraception, 2011 Feb 12; 83(3). PMID: 21310281
Flavones inhibit breast cancer proliferation through the Akt/FOXO3a signaling pathway.
Chia-Hung Lin, Ching-Yao Chang, +3 authors, Lei Wan.
BMC Cancer, 2015 Dec 18; 15. PMID: 26675309    Free PMC article.
Linking DNA Damage and Hormone Signaling Pathways in Cancer.
Matthew J Schiewer, Karen E Knudsen.
Trends Endocrinol Metab, 2016 Mar 06; 27(4). PMID: 26944914    Free PMC article.
Demographic Disparities in Late-Stage Diagnosis of Breast and Colorectal Cancers Across the USA.
Lee R Mobley, Tzy-Mey Kuo.
J Racial Ethn Health Disparities, 2016 Apr 14; 4(2). PMID: 27072541    Free PMC article.
Baby Boomers and Birth Certificates: Early-Life Socioeconomic Status and Cancer Risk in Adulthood.
Antoinette M Stroup, Kimberly A Herget, +6 authors, Ken R Smith.
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Breast Cancer Metastasis Associations with Clinicopathological Characteristics in Mexican Women Younger than 40 Years of Age
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Breast cancer treatment costs in younger, privately insured women.
Benjamin T Allaire, Donatus U Ekwueme, +4 authors, Justin G Trogdon.
Breast Cancer Res Treat, 2017 Apr 23; 164(2). PMID: 28432514    Free PMC article.
Fertility Preservation in Cancer Patients: In Vivo and In Vitro Options.
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Cell J, 2017 Jul 04; 19(2). PMID: 28670510    Free PMC article.
Preoperative [18]fluorodeoxyglucose-positron emission tomography/computed tomography in early stage breast cancer: Rates of distant metastases.
Vincent Vinh-Hung, Hendrik Everaert, +8 authors, Nam P Nguyen.
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Neural crest state activation in NRAS driven melanoma, but not in NRAS-driven melanocyte expansion.
Alicia M McConnell, Jeffrey K Mito, +4 authors, Leonard I Zon.
Dev Biol, 2018 Jun 09; 449(2). PMID: 29883661    Free PMC article.
Metastatic and triple-negative breast cancer: challenges and treatment options.
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Drug Deliv Transl Res, 2018 Jul 07; 8(5). PMID: 29978332    Free PMC article.
Highly Cited. Review.
Adverse reproductive health outcomes in a cohort of young women with breast cancer exposed to systemic treatments.
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Clinicopathological Characteristics And Treatment Outcomes Of Breast Cancer Among Adolescents And Young Adults In A Developing Country.
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MiR-1285-5p/TMEM194A axis affects cell proliferation in breast cancer.
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Where youth matters-clinicopathologic characteristics and emerging trends in treatment and outcomes in young Irish women with breast cancer.
Megan Greally, Jennifer Kielty, +11 authors, Janice M Walshe.
Ir J Med Sci, 2018 May 17; 188(1). PMID: 29766409
Age-related differences in breast cancer mortality according to race/ethnicity, insurance, and socioeconomic status.
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PD-L1 Expression and Tumor-infiltrating Lymphocytes in Breast Cancer: Clinicopathological Analysis in Women Younger than 40 Years Old.
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Does Age Matter? Estimating Risks of Locoregional Recurrence After Breast-conservative Surgery.
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Medicinal Herbs Used in Traditional Management of Breast Cancer: Mechanisms of Action.
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Young Patients with Hormone Receptor-Positive Breast Cancer Have a Higher Long-Term Risk of Breast Cancer Specific Death.
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Longitudinal effect of emotional processing on psychological symptoms in women under 50 with breast cancer.
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Young-onset breast cancer: a poor prognosis only exists in low-risk patients.
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Recurrence rates and long-term survival factors in young women with breast cancer.
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