Abstract
Women with metastatic breast cancer remains a heterogeneous group of patients with
different prognostic outcomes and therapeutic needs. Young women with de novo metastatic breast cancer (dnMBC) represent a peculiar population with respect to
tumor biology, prognosis, clinical management and survivorship issues. Overall, these
patients are able to attain long-term survival with a proper management of both primary
tumor and distant metastases. On the other hand, they are also at higher risk of experiencing
a deterioration in their quality of life (QoL) due to primary cancer-related side
effects. Young women are also likely to harbor germline pathogenic variants in cancer
predisposition genes which could affect treatment decisions and have a direct impact
on the lives of patients’ relatives. The loco-regional management of the primary tumor
represents another thorny subject, as the surgical approach has shown controversial
effects on the survival and the QoL of these patients.
This review aims to provide an update on these issues to better inform the clinical
management of dnMBC in young women.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Clinical Breast CancerAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Contemporary outcomes of metastatic breast cancer among 22,000 women from the multicentre ESME cohort 2008–2016.Eur J Cancer. 2020; 129: 60-70https://doi.org/10.1016/j.ejca.2020.01.016
- Survival differences among women with de novo stage IV and relapsed breast cancer.Ann Oncol. 2010; 21: 2169-2174https://doi.org/10.1093/annonc/mdq220
- Survival and disease characteristics of de novo versus recurrent metastatic breast cancer in a cohort of young patients.Br J Cancer. 2020; 122: 1618-1629https://doi.org/10.1038/s41416-020-0784-z
- Differential presentation and survival of de novo and recurrent metastatic breast cancer over time: 1990–2010.Breast Cancer Res Treat. 2018; 167: 579-590https://doi.org/10.1007/s10549-017-4529-5
- Impact of age at diagnosis of metastatic breast cancer on overall survival in the real-life ESME metastatic breast cancer cohort.Breast. 2020; 52: 50-57https://doi.org/10.1016/j.breast.2020.04.009
- Factors associated with early mortality among patients with de novo metastatic breast cancer: a population-based study.Oncologist. 2017; 22: 386-393https://doi.org/10.1634/theoncologist.2016-0369
- A nomogram for predicting survival in patients with de novo metastatic breast cancer: a population-based study.BMC Cancer. 2020; 20: 982https://doi.org/10.1186/s12885-020-07449-1
- Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression.J Clin Oncol. 2008; 26: 3324-3330https://doi.org/10.1200/JCO.2007.14.2471
- Subtype-dependent relationship between young age at diagnosis and breast cancer survival.J Clin Oncol. 2016; 34: 3308-3314https://doi.org/10.1200/JCO.2015.65.8013
- 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5).Ann Oncol. 2020; 31: 1623-1649https://doi.org/10.1016/j.annonc.2020.09.010
- ESO-ESMO 4th international consensus guidelines for breast cancer in young women (BCY4).Ann Oncol. 2020; (Published online)https://doi.org/10.1016/j.annonc.2020.03.284
- Fertility preservation and post-treatment pregnancies in post-pubertal cancer patients: ESMO Clinical Practice Guidelines†.Ann Oncol. 2020; 31: 1664-1678https://doi.org/10.1016/j.annonc.2020.09.006
- Trends in Metastatic Breast and prostate cancer — Lessons in cancer dynamics.N Engl J Med. 2015; 373: 1685-1687https://doi.org/10.1056/NEJMp1510443
- Why has breast cancer screening failed to decrease the incidence of de novo stage IV disease?.Cancers. 2019; 11: 500https://doi.org/10.3390/cancers11040500
- Age at diagnosis in relation to survival following breast cancer: a cohort study.World J Surg Oncol. 2015; 13https://doi.org/10.1186/s12957-014-0429-x
- Incidence of breast cancer with distant involvement among women in the United States, 1976 to 2009.JAMA. 2013; 309: 800-805https://doi.org/10.1001/jama.2013.776
- Low overall survival in women with de novo metastatic breast cancer: does this reflect tumor biology or a lack of access to health care?.JCO Global Oncol. 2020; : 679-687https://doi.org/10.1200/JGO.19.00408
- Clinicopathologic factors associated with de novo metastatic breast cancer.Pathol - Res Pract. 2016; 212: 1167-1173https://doi.org/10.1016/j.prp.2016.09.007
- The contribution of clinical subtype to survival differences among patients with de novo and recurrent metastatic breast cancer (dMBC).J Clin Oncol. 2020; 38: 1030https://doi.org/10.1200/JCO.2020.38.15_suppl.1030
- Twenty-years experience with de novo metastatic breast cancer: De novo metastatic breast cancer.Int J Cancer. 2015; 137: 1417-1426https://doi.org/10.1002/ijc.29503
- De Novo versus recurrent HER2-positive metastatic breast cancer: patient characteristics, treatment, and survival from the SystHERs Registry.Oncologist. 2020; 25: e214-e222https://doi.org/10.1634/theoncologist.2019-0446
- Prognosis of metastatic breast cancer: are there differences between patients with de novo and recurrent metastatic breast cancer?.Br J Cancer. 2015; 112: 1445-1451https://doi.org/10.1038/bjc.2015.127
- The effect of age on delay in diagnosis and stage of breast cancer.Oncologist. 2012; 17: 775-782https://doi.org/10.1634/theoncologist.2011-0469
- Breast Carcinomas Arising at a Young Age: Unique Biology or a Surrogate for Aggressive Intrinsic Subtypes?.J Clin Oncol. 2011; 29: e18-e20https://doi.org/10.1200/JCO.2010.28.9199
- Impact of subtype on survival of young patients with Stage IV breast cancer.Clin Breast Cancer. 2019; 19: 200-207.e1https://doi.org/10.1016/j.clbc.2019.01.005
- Age-Specific Differences in Oncogenic Pathway Deregulation Seen in Human Breast Tumors. Wu X, ed.PLoS One. 2008; 3: e1373https://doi.org/10.1371/journal.pone.0001373
- Biology of breast cancer in young women.Breast Cancer Res. 2014; 16: 427https://doi.org/10.1186/s13058-014-0427-5
- Elucidating Prognosis and Biology of Breast Cancer Arising in Young Women Using Gene Expression Profiling.Clin Cancer Res. 2012; 18: 1341-1351https://doi.org/10.1158/1078-0432.CCR-11-2599
- Tumour biomarker expression relative to age and molecular subtypes of invasive breast cancer.Br J Cancer. 2012; 107: 382-387https://doi.org/10.1038/bjc.2012.219
- The molecular landscape of premenopausal breast cancer.Breast Cancer Res. 2015; 17: 104https://doi.org/10.1186/s13058-015-0618-8
- Clinical utility of genomic signatures in young breast cancer patients: a systematic review.npj Breast Cancer. 2020; 6https://doi.org/10.1038/s41523-020-00188-3
- Supervised risk predictor of breast cancer based on intrinsic subtypes.J Clin Oncol. 2009; 27: 1160-1167https://doi.org/10.1200/JCO.2008.18.1370
- Prediction of Response to Neoadjuvant Chemotherapy Using Core Needle Biopsy Samples with the Prosigna Assay.Clin Cancer Res. 2016; 22: 560-566https://doi.org/10.1158/1078-0432.CCR-15-0630
- Research-based PAM50 subtype predictor identifies higher responses and improved survival outcomes in HER2-positive breast cancer in the NOAH study.Clin Cancer Res. 2014; 20: 511-521https://doi.org/10.1158/1078-0432.CCR-13-0239
- Correlative biomarker analysis of intrinsic subtypes and efficacy across the MONALEESA Phase III studies.J Clin Oncol. 2021; 39: 1458-1467https://doi.org/10.1200/JCO.20.02977
- Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer.N Engl J Med. 2019; 380: 1929-1940https://doi.org/10.1056/NEJMoa1813904
- Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies.J Clin Invest. 2011; 121: 2750-2767https://doi.org/10.1172/JCI45014
- Refinement of triple-negative breast cancer molecular subtypes: implications for neoadjuvant chemotherapy selection.PLoS One. 2016; 11e0157368https://doi.org/10.1371/journal.pone.0157368
- Programmed cell death ligand 1 in breast cancer: technical aspects, prognostic implications, and predictive value.Oncologist. 2019; 24: e1055-e1069https://doi.org/10.1634/theoncologist.2019-0197
- Determining PD-L1 status in patients with triple-negative breast cancer: lessons learned from IMpassion130.J Natl Cancer Inst. 2021; (Published online): djab121https://doi.org/10.1093/jnci/djab121
- Reproductive potential and performance of fertility preservation strategies in BRCA-mutated breast cancer patients.Ann Oncol. 2018; 29: 237-243https://doi.org/10.1093/annonc/mdx639
- BRCA 1 and 2 mutation status: the elephant in the room during oncofertility counseling for young breast cancer patients.Ann Oncol. 2018; 29: 26-28https://doi.org/10.1093/annonc/mdx777
- Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial.Nat Med. 2018; 24: 628-637https://doi.org/10.1038/s41591-018-0009-7
- Classifications within Molecular Subtypes Enables Identification of BRCA1/BRCA2 Mutation Carriers by RNA Tumor Profiling. Prokunina-Olsson L, ed.PLoS One. 2013; 8: e64268https://doi.org/10.1371/journal.pone.0064268
- Clinical behavior and outcomes of breast cancer in young women with germline BRCA pathogenic variants.NPJ Breast Cancer. 2021; 7: 16https://doi.org/10.1038/s41523-021-00224-w
- Rethinking screening for breast cancer and prostate cancer.JAMA. 2009; 302: 1685-1692https://doi.org/10.1001/jama.2009.1498
- Effect of three decades of screening mammography on breast-cancer incidence.N Engl J Med. 2012; 367: 1998-2005https://doi.org/10.1056/NEJMoa1206809
- Genomic characterization of de novo metastatic breast cancer.Clin Cancer Res. 2020; (Published online)https://doi.org/10.1158/1078-0432.CCR-20-1720
- c-Myb enhances breast cancer invasion and metastasis through the Wnt/β-Catenin/Axin2 pathway.Cancer Res. 2016; 76: 3364-3375https://doi.org/10.1158/0008-5472.CAN-15-2302
- The clinicomolecular landscape of de novo versus relapsed stage IV metastatic breast cancer.Exp Mol Pathol. 2020; 114104404https://doi.org/10.1016/j.yexmp.2020.104404
- Targeted therapy for premenopausal women with HR + , HER2 − advanced breast cancer: focus on special considerations and latest advances.Clin Cancer Res. 2018; 24: 5206-5218https://doi.org/10.1158/1078-0432.CCR-18-0162
- Does guideline non-adherence result in worse clinical outcomes for hormone receptor-positive and HER2-negative metastatic breast cancer in premenopausal women?: result of an institution database from South Korea.BMC Cancer. 2019; 19: 84https://doi.org/10.1186/s12885-018-5258-9
- Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial.Lancet Oncol. 2018; 19: 904-915https://doi.org/10.1016/S1470-2045(18)30292-4
- Phase III randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-Negative Advanced Breast Cancer: MONALEESA-3.J Clin Oncol. 2018; 36: 2465-2472https://doi.org/10.1200/JCO.2018.78.9909
- Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial.Lancet Oncol. 2016; 17: 425-439https://doi.org/10.1016/S1470-2045(15)00613-0
- Palbociclib and Letrozole in Advanced Breast Cancer.N Engl J Med. 2016; 375: 1925-1936https://doi.org/10.1056/NEJMoa1607303
- MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer.J Clin Oncol. 2017; 35: 3638-3646https://doi.org/10.1200/JCO.2017.75.6155
- MONARCH 2: Abemaciclib in Combination With Fulvestrant in Women With HR+/HER2- Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy.J Clin Oncol. 2017; 35: 2875-2884https://doi.org/10.1200/JCO.2017.73.7585
- Overall Survival of CDK4/6-Inhibitor–Based Treatments in Clinically Relevant Subgroups of Metastatic Breast Cancer: Systematic Review and Meta-Analysis.J Natl Cancer Inst. 2020; 112: 1089-1097https://doi.org/10.1093/jnci/djaa071
- Palbociclib plus exemestane with gonadotropin-releasing hormone agonist versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (KCSG-BR15-10): a multicentre, open-label, randomised, phase 2 trial.Lancet Oncol. 2019; 20: 1750-1759https://doi.org/10.1016/S1470-2045(19)30565-0
- Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation.N Engl J Med. 2017; 377: 523-533https://doi.org/10.1056/NEJMoa1706450
- Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation.N Engl J Med. 2018; 379: 753-763https://doi.org/10.1056/NEJMoa1802905
- OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer.Ann Oncol. 2019; 30: 558-566https://doi.org/10.1093/annonc/mdz012
- Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial.Ann Oncol. 2020; 31: 1526-1535https://doi.org/10.1016/j.annonc.2020.08.2098
- Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): a randomised, double-blind, placebo-controlled, phase 3 trial.Lancet Oncol. 2020; 21: 1269-1282https://doi.org/10.1016/S1470-2045(20)30447-2
- TBCRC 048: phase II study of olaparib for metastatic breast cancer and mutations in homologous recombination-related genes.J Clin Oncol. 2020; 38: 4274-4282https://doi.org/10.1200/JCO.20.02151
- Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer.N Engl J Med. 2018; 379: 2108-2121https://doi.org/10.1056/NEJMoa1809615
- Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial.Lancet. 2020; 396: 1817-1828https://doi.org/10.1016/S0140-6736(20)32531-9
- Controversies in Oncology: Surgery of the primary tumour in patients presenting with de novo metastatic breast cancer: to do or not to do?.ESMO Open. 2018; 3https://doi.org/10.1136/esmoopen-2018-000324
- Does aggressive local therapy improve survival in metastatic breast cancer?.Surgery. 2002; 132 (discussion 626-627): 620-626https://doi.org/10.1067/msy.2002.127544
- Surgical resection of the primary tumour is associated with improved survival in patients with distant metastatic breast cancer at diagnosis.Eur J Surg Oncol. 2009; 35: 1146-1151https://doi.org/10.1016/j.ejso.2009.03.012
- Surgery of the primary tumor does not improve survival in stage IV breast cancer.Breast Cancer Res Treat. 2011; 129: 459-465https://doi.org/10.1007/s10549-011-1648-2
- Surgical resection of the primary tumor is associated with increased long-term survival in patients with stage IV breast cancer after controlling for site of metastasis.Ann Surg Oncol. 2007; 14: 3345-3351https://doi.org/10.1245/s10434-007-9527-0
- Surgery of primary tumors in stage IV breast cancer: an updated meta-analysis of published studies with meta-regression.Med Oncol. 2012; 29: 3282-3290https://doi.org/10.1007/s12032-012-0310-0
- A randomized phase III trial of systemic therapy plus early local therapy versus systemic therapy alone in women with de novo stage IV breast cancer: A trial of the ECOG-ACRIN Research Group (E2108).J Clin Oncol. 2020; 38: LBA2https://doi.org/10.1200/JCO.2020.38.18_suppl.LBA2
- Locoregional treatment versus no treatment of the primary tumour in metastatic breast cancer: an open-label randomised controlled trial.Lancet Oncol. 2015; 16: 1380-1388https://doi.org/10.1016/S1470-2045(15)00135-7
- Randomized trial comparing resection of primary tumor with no surgery in stage IV breast cancer at presentation: protocol MF07-01.Ann Surg Oncol. 2018; 25: 3141-3149https://doi.org/10.1245/s10434-018-6494-6
- Impact of breast surgery in primary metastasized breast cancer: outcomes of the prospective randomized phase III ABCSG-28 POSYTIVE trial.Ann Surg. 2019; 269: 1163-1169https://doi.org/10.1097/sla.0000000000002771
- Quality-of-life scores predict outcome in metastatic but not early breast cancer. International Breast Cancer Study Group.J Clin Oncol. 2000; 18: 3768-3774https://doi.org/10.1200/JCO.2000.18.22.3768
- Addressing the Survivorship Care Needs of Patients Receiving Extended Cancer Treatment.Am Soc Clin Oncol Educ Book. 2017; 37: 674-683https://doi.org/10.1200/EDBK_175673
- Traumatic stress, life events, and emotional support in women with metastatic breast cancer: cancer-related traumatic stress symptoms associated with past and current stressors.Health Psychol. 1999; 18: 555-560https://doi.org/10.1037//0278-6133.18.6.555
- Effect of age and race upon quality of life of young breast cancer survivors.Clin Breast Cancer. 2014; 14: e21-e31https://doi.org/10.1016/j.clbc.2013.10.003
- Explaining age-related differences in depression following breast cancer diagnosis and treatment.Breast Cancer Res Treat. 2012; 136: 581-591https://doi.org/10.1007/s10549-012-2277-0
- Uncertainty, lack of control and emotional functioning in women with metastatic breast cancer: a review and secondary analysis of the literature using the critical appraisal technique.Eur J Cancer Care (Engl). 2010; 19: 564-574https://doi.org/10.1111/j.1365-2354.2010.01215.x
- Prospective study of fertility concerns and preservation strategies in young women with breast cancer.J Clin Oncol. 2014; 32: 1151-1156https://doi.org/10.1200/JCO.2013.52.8877
- Gender-specific aspects related to type of fertility preservation strategies and access to fertility care.ESMO Open. 2020; 5e000771https://doi.org/10.1136/esmoopen-2020-000771
- ESHRE guideline: female fertility preservation†.Hum Repro Open. 2020; (2020(hoaa052))https://doi.org/10.1093/hropen/hoaa052
- Posttraumatic stress disorder following cancer. A conceptual and empirical review.Clin Psychol Rev. 2002; 22: 499-524https://doi.org/10.1016/s0272-7358(01)00118-0
- Psychological interventions for women with metastatic breast cancer.Cochrane Database Syst Rev. 2013; CD004253https://doi.org/10.1002/14651858.CD004253.pub4
- Targeting depressive symptoms in younger breast cancer survivors: A randomized controlled trial of mindfulness meditation and survivorship education.San Antonio Breast Cancer Symopsium. 2020; (Abstract GS2-10)
- Health-related quality of life in premenopausal women with hormone-receptor-positive, HER2-negative advanced breast cancer treated with ribociclib plus endocrine therapy: results from a phase III randomized clinical trial (MONALEESA-7).Ther Adv Med Oncol. 2020; 121758835920943065https://doi.org/10.1177/1758835920943065
- Patient-Reported Outcomes of Palbociclib Plus Exemestane with GnRH Agonist versus Capecitabine in Premenopausal Women with Hormone Receptor-Positive Metastatic Breast Cancer: A Prospective, Open-Label, Randomized Phase ll Trial (KCSG-BR 15-10).Cancers (Basel). 2020; 12https://doi.org/10.3390/cancers12113265
- Premature menopause in young breast cancer: effects on quality of life and treatment interventions.J Thorac Dis. 2013; 5: S55-S61https://doi.org/10.3978/j.issn.2072-1439.2013.06.20
- Discussing motherhood when the oncological prognosis is dire: ethical considerations for physicians.ESMO Open. 2020; 5https://doi.org/10.1136/esmoopen-2020-000956
- Evidence-based approaches for the management of side-effects of adjuvant endocrine therapy in patients with breast cancer.Lancet Oncol. 2021; 22: e303-e313https://doi.org/10.1016/S1470-2045(20)30666-5
Article info
Publication history
Published online: October 08, 2021
Accepted:
October 3,
2021
Received in revised form:
September 17,
2021
Received:
March 8,
2021
Identification
Copyright
© 2021 Elsevier Inc. All rights reserved.
