EDITORIAL URRENT C OPINION

Breast cancer in young women: challenges, progress, and barriers Shani Paluch-Shimon a and Ellen Warner b

Breast cancer is the leading cause of cancer death among women worldwide [1]. Breast cancer in young women is uncommon, with a cumulative risk for developing breast cancer by age 40 of approximately 0.5%. However, in contrast to women aged 40 and over who have a four-fold greater risk of breast cancer in developed as compared with developing countries, there is little difference worldwide in the incidence of breast cancer in women under age 40 [2]. Consequently, while breast cancer in women under age 40 represents just over 5% of all breast cancer cases in developed countries, it represents a much higher proportion of cases in middle-income and low-income countries. Moreover, in highincome countries, breast cancer is the leading cause of death among women under the age of 45 years, following road traffic accidents and self-injury, making breast cancer in young women a significant public health issue [3]. Particularly disturbing are several reports suggesting a recent rise in the incidence of breast cancer in younger women. A study published by Bouchardy et al. [4] reported a significant increase in breast cancer incidence among 25–39-year-old women in Geneva: from 19.7 per 100 000 in 1995 to 53.9 per 100 000 in 2004, with the main increase occurring during the years 2002 2004. Pollan et al. [5] also reported a steady increase in breast cancer incidence among 25 44-year-old Spanish women between 1980 and 2004, with an annual increase in incidence of 1.7% . One can only speculate whether this increase is related to changes in putative risk factors such as the decrease in the average age of menarche, delayed childbearing, or increased alcohol consumption among adolescent and young adult women. Breast cancer in young women exhibits adverse clinical and pathological features more often than breast cancer diagnosed in older women. As breast cancer screening is not indicated in this young population, and because of intrinsically more aggressive tumour biology, young breast cancer patients are diagnosed with larger tumours, greater lymph-node involvement, higher histological grade, higher proliferation index, and more www.supportiveandpalliativecare.com

lympho-vascular invasion than their older counterparts. A greater proportion of breast cancer in young women are triple-negative (oestrogen and progesterone receptor negative and without HER2/ neu overexpression) and, a greater proportion have HER2/neu overexpression, according to most studies [6–13]. Younger women are more likely to receive chemotherapy than older patients and are more likely to require mastectomy than lumpectomy. Among patients harbouring a BRCA1 or a BRCA2 mutation, breast cancer is diagnosed at a younger age and has distinct clinic-pathological characteristics [14–16]. Breast cancer in young women is associated with worse outcome, specifically, increased local and distance recurrence and poorer survival [9,17–19]. The literature remains divided whether age is in itself an independent risk factor or whether the poor outcome is a result of more advanced stage at diagnosis and more adverse biology [11,20]. A germline mutation in either the BRCA1 or the BRCA2 genes is the most significant known risk factor for developing early onset breast cancer [21,22]. The presence of a heritable genetic mutation further compounds what is already a challenging situation clinically and psychologically, particularly for young women already faced with many daunting decisions with respect to surgery, fertility, and premature menopause. Breast cancer in women under 40 years of age is a devastating and complex disease. It strikes these women when they are at the peak of their reproductive years, struggling to establish and balance family life and careers, and at a time when they have many years ahead of them to suffer the ramifications a Fellow of the Dr Pinchas Borenstein Talpiot Medical Leadership Program. Breast Cancer Service for Young Women, Breast Oncology Institute, Division of Oncology, Sheba Medical Centre, Tel Hashomer, Israel and bSunnybrook Health Sciences Centre, Toronto, Canada

Correspondence to Ellen Warner, Sunnybrook Health Sciences Centre, Toronto, Canada. E-mail: [email protected]; [email protected] Curr Opin Support Palliat Care 2015, 9:268–270 DOI:10.1097/SPC.0000000000000152 Volume 9  Number 3  September 2015

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Breast cancer in young women Paluch-Shimon and Warner

of recurrent disease and/or long-term effects of treatment. They are more likely than older women to be concerned with appearance, attractiveness, and body image, which put them at greater risk of psychological distress [23]. Facing premature menopause and sexual dysfunction following treatment is also of great concern for younger breast cancer patients. Many of them would like to begin or expand their families after treatment, yet fertility is often impaired by treatment. Further research is needed on all aspects of breast cancer in young women. With the exception of the minority of cancers that can be attributed to highly penetrant inherited genetic mutations that greatly elevate the risk of early onset breast cancer, the cause of breast cancer in young women is poorly understood. In most breast cancer clinical trials, the great majority of women are over the age of 40, thus little evidence-based data are available about the optimal management of young women with this disease. Encouragingly, in recent years, there have been more and more clinical trials devoted to young women with breast cancer, and the first international consensus guidelines for the care of young women with breast cancer was published in 2014 [24]. This issue of Current Opinion in Supportive and Palliative Care aims to provide an overview of the many complex issues that arise in the supportive management of young women with breast cancer that are either unique or particularly relevant to this age group. Thus, there is a focus on age-specific psychosocial problems and on the sequelae of premature ovarian failure. Special emphasis has been placed on recent publications and on studies of interventions. The first article in this section by Fergus et al. [25], so aptly subtitled: ‘The Minority Group with the Majority of Need’, gives a broad yet detailed overview of the numerous psychosocial challenges faced by young women with breast cancer, including a thorough review of the relevant literature, and highlights gaps that need to be addressed. Complementing this article is the review by FernandesTaylor et al. [26] which describes psychosocial interventions to help young women during active treatment, a period when these previously healthy young women must not only suddenly confront the threat of mortality, but must also make multiple complicated and stressful decisions. Some of the most difficult of these decisions relate to whether to undergo fertility preservation prior to starting systemic therapy and, if so, which procedure(s) to undergo. A state-of-the art discussion of these options, and the many uncertainties still surrounding them, appears in the review by Ronn et al. [27].

But, even women fortunate enough to have completed their families prior to their breast cancer diagnosis will almost certainly have to deal with the physically and psychologically disabling symptoms of breast surgery as well as ovarian damage and/or suppression from chemotherapy and hormonal therapy. Perhaps, most prominent among these symptoms are sexual dysfunction and disturbance of body image. Management of these issues is ably reviewed in the article by Zhou et al. [28]. Despite enduring the major and often permanent toxicities of aggressive therapies given with curative intent, a disproportionate number of these young women will, unfortunately, develop metastatic disease. Nevertheless, prolonged survival with excellent quality of life can often be achieved in this population with sequential palliative systemic therapies, as discussed in the article by Eng et al. [29]. The authors of these review articles come from a diverse professional background, reflecting one of the most important issues in caring for these young patients – the significance of multidisciplinary care. However, a further step up from multidisciplinary care is the establishment of dedicated young women’s programs, as thoroughly reviewed in this issue by Villarreal-Garza et al. [30]. We have had the privilege of having such programs at our own cancer centres and observing first-hand the many benefits such a program provides. Finally, we wish to thank Sunbul Akhtar and the staff at Current Opinion in Supportive and Palliative Care for providing us with the opportunity to be co-editors for this issue. Acknowledgements We wish to thank Sunbul Akhtar for her professionalism on all matters pertaining to the publication of this issue. Financial support and sponsorship None. Conflicts of interest There are no conflicts of interest.

REFERENCES 1. Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010; 127:2893–2917. 2. Assi HA, Khoury KE, Dbouk H, et al. Epidemiology and prognosis of breast cancer in young women. J Thorac Dis 2013; 5 (Suppl 1):S2–S8. 3. World Health Organization. Women & Health. Geneva: WHO Press; 2009. 4. Bouchardy C, Fioretta G, Verkooijen HM, et al. Recent increase of breast cancer incidence among women under the age of forty. Br J Cancer 2007; 96:1743–1746. 5. Pollan M, Pastor-Barriuso R, Ardanaz E, et al. Recent changes in breast cancer incidence in Spain, 1980–2004. J Natl Cancer Inst 2009; 101:1584–1591. 6. Colleoni M, Rotmensz N, Robertson C, et al. Very young women (

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