To update guidance for health care providers about fertility preservation for adults and children with cancer.
A systematic review of the literature published from March 2006 through January 2013 was ...completed using MEDLINE and the Cochrane Collaboration Library. An Update Panel reviewed the evidence and updated the recommendation language.
There were 222 new publications that met inclusion criteria. A majority were observational studies, cohort studies, and case series or reports, with few randomized clinical trials. After review of the new evidence, the Update Panel concluded that no major, substantive revisions to the 2006 American Society of Clinical Oncology recommendations were warranted, but clarifications were added.
As part of education and informed consent before cancer therapy, health care providers (including medical oncologists, radiation oncologists, gynecologic oncologists, urologists, hematologists, pediatric oncologists, and surgeons) should address the possibility of infertility with patients treated during their reproductive years (or with parents or guardians of children) and be prepared to discuss fertility preservation options and/or to refer all potential patients to appropriate reproductive specialists. Although patients may be focused initially on their cancer diagnosis, the Update Panel encourages providers to advise patients regarding potential threats to fertility as early as possible in the treatment process so as to allow for the widest array of options for fertility preservation. The discussion should be documented. Sperm and embryo cryopreservation as well as oocyte cryopreservation are considered standard practice and are widely available. Other fertility preservation methods should be considered investigational and should be performed by providers with the necessary expertise.
Breast cancer arising at a young age is relatively uncommon, particularly in the developed world. Several studies have demonstrated that younger patients often experience a more aggressive disease ...course and have poorer outcome compared to older women. Expression of key biomarkers, including endocrine receptors, HER2 and proliferation markers, appears to be different in younger patients and young women are more likely to harbor a genetic predisposition. Despite these differences, little research to date has focused on the biology of these tumors to refine prognosis, and potentially direct treatment strategies, which remain similar to those offered to older patients. Accumulating evidence suggests the differences in breast stroma in younger patients and changes that occur with pregnancy and breastfeeding likely contribute to the different biology of these tumors. Reproductive behaviors appear to impact the biology of tumors developing later in life. In addition, tumors arising during or shortly following pregnancy appear to exhibit unique biological features. In this review, we discuss our emerging understanding of the biology of breast cancer arising at a young age at both the pathologic and the genomic level. We elucidate the potential role of genomic signatures, the impact of pregnancy and breastfeeding on breast cancer biology, and how even current knowledge might advance the clinical management of young breast cancer patients.
The growing availability of more effective therapies has contributed to an increased survival of patients with breast cancer. In hormone receptor-positive early disease, increased survival is ...strongly correlated with the use of adjuvant endocrine therapy, but this therapy can cause side-effects that have major consequences in terms of treatment adherence and patients' quality of life. In premenopausal breast cancer survivors, these side-effects might be even more prominent due to the abrupt suppression of oestrogen associated with the most intense endocrine therapies. An important ambition of cancer care in the 21st century is to recover pre-cancer quality of life and emotional and social functions, which is only possible through the mitigation of the side-effects of anticancer treatments. This Review presents a comprehensive summary of the efficacy and safety data of the available interventions (hormonal and non-hormonal pharmacological strategies, non-pharmacological approaches, and complementary and alternative medicine) to control selected side-effects associated with adjuvant endocrine therapy (hot flashes, sexual dysfunction, weight gain, musculoskeletal symptoms, and fatigue), providing updated, evidence-based approaches for their management.
Women under 40 years old are at increased risk for developing human epidermal growth factor receptor 2 (HER2) positive or triple negative subtype and more advanced breast cancer, yet young age itself ...has also historically been an independent prognostic factor.
Using the Surveillance, Epidemiology, and End Results (SEER) Program, we examined data for 271,173 women with stage I-III breast cancer between 2010 and 2015. Using Fine and Gray regression models to account for competing risks, we examined the risk of breast cancer-specific death by age and clinical subtypes, considering grade, hormone receptor (HR) and HER2 status, adjusting for demographic, clinical and treatment variables.
Of 271,173 women eligible for analysis, 14,109 were <40 years of age. Women under 40 years old were more likely to be non-white, uninsured, and to have higher stage, higher grade, HER2-positive and triple-negative subtype disease (all, p < 0.001). Compared to women ages 40–60, women ages <40 had higher breast cancer mortality (hazard ratio, 1.8; 95% confidence interval (CI) 1.6–1.9) in unadjusted analysis. In models controlling for demographic, clinical and treatment factors, young age was significantly associated with an increased risk of breast cancer mortality among women with HR-positive, lower grade disease (hazard ratio 1.7; 95% CI 1.4–2.1) but not for women with high grade/HR-positive, HER2-positive, or triple-negative disease. Women age >75 had increased breast cancer mortality in all subtypes.
With modern clinical subtyping, age under 40 remains independently associated with worse outcomes in 30 months follow-up only in HR-positive, lower grade disease.
•Young women present with more advanced and aggressive types of breast cancer.•Young age is not an independent prognostic factor in HER2+ breast cancer or TNBC.•Young age is independently associated with poor outcomes in HR+/lower grade disease.
•In premenopausal cancer patients, chemotherapy can cause premature ovarian insufficiency (POI).•GnRHa administration during chemotherapy is an available strategy to reduce POI risk.•This strategy is ...now endorsed for clinical use by several guidelines.•Long-term follow-up data from the available randomized trials is awaited.•The protective mechanism of action of this strategy remains not clearly identified.•Adequately conducted in vitro and in vivo animal experiments should be further encouraged.
Survivorship issues are an area of crucial importance to be addressed as early as possible by all health care providers dealing with cancer patients. In women diagnosed during their reproductive years, the possible occurrence of chemotherapy-induced premature ovarian insufficiency (POI) is of particular concern being associated with important menopause-related symptoms, psychosocial issues as well as infertility. Temporary ovarian suppression by administering a gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy has been studied to reduce the gonadotoxic impact of chemotherapy thus diminishing the chance of developing POI. Despite more than 30 years of research in both preclinical and clinical settings, the performance of this strategy has remained highly debated until recently. In particular, the potential mechanisms of action for the protective effects of GnRHa during chemotherapy are still not clearly identified. Nevertheless, important novel research efforts in the field have better elucidated the role of this option that is now endorsed for clinical use by several guidelines.
This manuscript aims at providing an extensive overview of the literature on the use of temporary ovarian suppression with GnRHa during chemotherapy in cancer patients by addressing its biological rationale, the available preclinical and clinical evidence as well as the still existing grey zones in this field that future research efforts should address.
The results of several studies aiming to tailor early breast cancer treatment to individual risk were released in 2023. Axillary lymph node dissections and radiotherapy may be safely omitted in ...carefully selected patients. Sustained benefit from adjuvant CDK4/6 inhibitors was observed in high-risk hormone receptor-positive disease and the addition of immunotherapy to neoadjuvant chemotherapy improved pathological response. Continued benefit from perioperative pembrolizumab was reported in patients with triple negative breast cancer, while atezolizumab did not improve the risk of recurrence either pre- or postoperatively. The chance of pregnancy was higher in younger patients attempting to conceive after breast cancer.
•Risk-adapted management of early breast cancer (BC) is becoming increasingly relevant.•Axillary dissections and radiotherapy may be safely omitted in carefully selected patients.•Adjuvant CDK4/6 inhibitors improved outcomes in high-risk hormone receptor-positive (HR+) BC.•Chemo-immunotherapy regimens increased the pathological response in HR + BC.•Pregnancy after breast cancer appears to be safe in patients with HR + disease and BRCA1/2 carriers.
Young women are at increased risk for developing more aggressive subtypes of breast cancer. Although previous studies have shown a higher risk of breast cancer recurrence and death among young women ...with early-stage breast cancer, they have not adequately addressed the role of tumor subtype in outcomes.
We examined data from women with newly diagnosed stage I to III breast cancer presenting to one of eight National Comprehensive Cancer Network centers between January 2000 and December 2007. Multivariable Cox proportional hazards models were used to assess the relationship between age and breast cancer-specific survival.
A total of 17,575 women with stage I to III breast cancer were eligible for analysis, among whom 1,916 were ≤ 40 years of age at diagnosis. Median follow-up time was 6.4 years. In a multivariable Cox proportional hazards model controlling for sociodemographic, disease, and treatment characteristics, women ≤ 40 years of age at diagnosis had greater breast cancer mortality (hazard ratio HR, 1.4; 95% CI, 1.2 to 1.7). In stratified analyses, age ≤ 40 years was associated with statistically significant increases in risk of breast cancer death among women with luminal A (HR, 2.1; 95% CI, 1.4 to 3.2) and luminal B (HR 1.4; 95% CI, 1.1 to 1.9) tumors, with borderline significance among women with triple-negative tumors (HR, 1.4; 95% CI, 1.0 to 1.8) but not among those with human epidermal growth factor receptor 2 subtypes (HR, 1.2; 95% CI, 0.8 to 1.9). In an additional model controlling for detection method, young age was associated with significantly increased risk of breast cancer death only among women with luminal A tumors.
The effect of age on survival of women with early breast cancer seems to vary by breast cancer subtype. Young age seems to be particularly prognostic in women with luminal breast cancers.
Purpose To provide current recommendations about fertility preservation for adults and children with cancer. Methods A systematic review of the literature published from January 2013 to March 2017 ...was completed using PubMed and the Cochrane Library. An Update Panel reviewed the identified publications. Results There were 61 publications identified and reviewed. None of these publications prompted a significant change in the 2013 recommendations. Recommendations Health care providers should initiate the discussion on the possibility of infertility with patients with cancer treated during their reproductive years or with parents/guardians of children as early as possible. Providers should be prepared to discuss fertility preservation options and/or to refer all potential patients to appropriate reproductive specialists. Although patients may be focused initially on their cancer diagnosis, providers should advise patients regarding potential threats to fertility as early as possible in the treatment process so as to allow for the widest array of options for fertility preservation. The discussion should be documented. Sperm, oocyte, and embryo cryopreservation are considered standard practice and are widely available. There is conflicting evidence to recommend gonadotrophin-releasing hormone agonists (GnRHa) and other means of ovarian suppression for fertility preservation. The Panel recognizes that, when proven fertility preservation methods are not feasible, and in the setting of young women with breast cancer, GnRHa may be offered to patients in the hope of reducing the likelihood of chemotherapy-induced ovarian insufficiency. GnRHa should not be used in place of proven fertility preservation methods. The panel notes that the field of ovarian tissue cryopreservation is advancing quickly and may evolve to become standard therapy in the future. Additional information is available at www.asco.org/survivorship-guidelines .
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