Fertility Preservation Methods in Breast Cancer

Thanks to the recent advances in reproductive medicine, more and more young women with breast cancer may be offered the possibility of preserving their fertility. Fertility can be endangered by chemotherapy, by treatment duration and by patient's age at diagnosis. The currently available means to preserve a young woman's fertility are pharmacological protection with gonadotrophin-releasing hormone analogues during chemotherapy, and ovarian tissue or oocyte/embryo freezing before treatment. New future venues, including in vitro maturation, will improve the feasibility and efficacy of the fertility preservation methods in breast cancer patients.     

Being Pregnant and Diagnosed with Breast Cancer

Breast cancer during pregnancy (BCP) is an important subgroup within the young and very young breast cancer patients. It accounts for about 1% of all breast cancers. Due to an increased awareness, the attitude towards breast cancer during pregnancy has changed and, today, women with BCP are more likely to receive standard chemotherapy and have a term delivery instead of being advised to interrupt the pregnancy or undergo an early preterm delivery. This increased knowledge is based on small cohort studies and international collaborations such as the registry by the German Breast Group for BCP and the initiative of the European Society of Gynaecological Oncology (ESGO). Guidelines and recommendations such as the German guidelines by the AGO (Arbeitsgemeinschaft Gynäkologische Onkologie, www.ago-online.org) and the National Comprehensive Cancer Network (NCCN) guidelines include recommendations for BCP. In general, surgery and chemotherapy (beyond the 13th week of gestation) can be safely performed during pregnancy. Chemotherapy should follow the treatment recommendations for breast cancer in young women. Trastuzumab, endocrine treatment, and radiotherapy are not indicated during pregnancy. Preterm delivery should be avoided as far as possible because it bears a higher risk of infant morbidity and mortality. The treatment of BCP should be planned within a multidisciplinary team including perinatologists, obstetricians and neonatologists.     

Can We Keep the ‘PROMISE’? AGO Breast Commission: Commentary on Recent Evidence Regarding LHRH Analogues for the Preservation of Ovarian Function

Recently reported data from the German ZORO trial and the Italian PROMISE-GIM6 trial have come to different conclusions. The AGO Breast Commission does not recommend the general use of luteinizing hormone-releasing hormone (LHRH) analogues for the preservation of ovarian function. Instead, we distinguish between patients with hormone receptor-negative and hormone receptor-positive disease. This article reviews the AGO recommendations in light of the ZORO and PROMISE-GIM6 data. In conclusion, separate recommendations are needed for the prevention of ovarian failure and for fertility preservation because the trials did not investigate fertility rate as a primary outcome measure. The results from not yet published trials such as OPTION and POEM may shed new light on the role of LHRH analogues.     

Breast Cancer in Women With Recent Exposure to Fertility Medications is Associated With Poor Prognostic Features

Background: Fertility drug therapy (FDT) induces supraphysiologic endogenous estrogen production and might transiently increase breast cancer risk. Tumors developing following FDT exposure have not been extensively studied.Methods: Thirty-eight breast cancer patients with 40 primary tumors and with history of FDT exposure were identified and compared with two other breast cancer groups: women with pregnancy-associated breast cancer (PABC, 22 patients with 23 tumors) and premenopausal women born during same calendar years and not exposed to hormonal manipulations or recent pregnancy (controls, 192 patients with 201 tumors). Patients were diagnosed and treated mostly during the last decade.Results: Compared with controls, tumors of patients with FDT exposure presented at advanced stages (P < .005), were more likely to be estrogen or progesterone receptor negative (P < .03) and of poor histology grade (P <.0002). Aggressive features predominated among women diagnosed within 2 years of an FDT cycle (P <.05). FDT and PABC groups shared similarities. With a median follow-up of 43 months, relapse-free and cancer-free survival rates were significantly reduced in the FDT and PABC groups (P < .01 and P < .01, respectively). Multivariate analysis revealed only treatment-defined tumor stage (operable, locally advanced, or metastatic) as predictive of survival (P < .0001).Conclusion: Breast tumors in women with recent FDT exposure present with poor prognostic features and share similarities with PABC. Survival is stage dependent.     

Pregnancy after Breast Cancer: Myths and Facts

Most young breast cancer survivors consider reproductive issues to be of great importance, but many questions remain undervalued and unanswered. Overall, available data support the safety and feasibility of pregnancy and breastfeeding after breast cancer. The accuracy of the evidence is however limited by: i) the retrospective and frequently incomplete population-based nature of the data, ii) data not representing the entire population, iii) patient-related effects, iv) underpowered sample size, and v) lack of control for biological factors and risk determinants. We review the available evidence in light of these limitations which outline the need for prospective data collection and focused priority research.     

Protroca: A Noninterventional Study on Prophylactic Lipegfilgrastim against Chemotherapy-Induced Neutropenia in Nonselected Breast Cancer Patients

BackgroundProtroca evaluated the efficacy and safety of primary and secondary prophylaxis of neutropenia with lipegfilgrastim (Lonquex®) in breast cancer patients receiving neoadjuvant or adjuvant chemotherapy (CT).Patients and MethodsOf the 255 patients enrolled, 248 patients were evaluable for the intent-to-treat (ITT) and 194 patients for the per-protocol set. Primary and secondary end points after lipegfilgrastim treatment were assessed.ResultsNine patients of the ITT set receiving lipegfilgrastim as primary prophylaxis (n = 222) had febrile neutropenia of grade 3–4 (5 patients) or infection of grade 3–4 (4 patients); 1/26 of those receiving secondary prophylaxis had an event. Dose reductions were performed in 9.5% of the patients. Postponement of cancer CT cycles for >3 days occurred in <15% of patients; 10.8% (92/851 AEs) and 8% (2/25 SAEs) of documented adverse events and serious adverse events, respectively, were related to lipegfilgrastim.ConclusionsApplication of lipegfilgrastim was effective as primary and secondary prophylaxis in the prevention of CT-induced neutropenia in breast cancer.     

妊娠期乳腺癌

目的：介绍妊娠期乳腺癌的研究进展。方法：复习近年来有关文献并进行综述。结果：妊娠期乳腺癌常被延误诊断，确诊主要靠穿刺细胞学检查和活检。治疗原则同一般乳腺癌，但需考虑胎儿因素；终止妊娠并不能改善预后。结论：妊娠期乳腺癌与普通乳腺癌相比，临床诊断更晚，预后更差，但与同年龄同期乳腺癌比较，两者的预后差异并不明显。早期乳腺癌患者治疗2年后可考虑再次妊娠。     

Fertility Preservation for Young Women with Rectal Cancer—A Combined Approach from One Referral Center

Background  Up to 6% of women with colorectal cancer are diagnosed in the reproductive age and are at risk for premature ovarian failure and infertility due to pelvic irradiation and chemotherapy. Study Design  Between 1997 and 2007, six women with rectal carcinoma were referred to the McGill Reproductive Center (Montreal, Canada) for fertility preservation. Following resection of their primary tumor, they were scheduled to undergo pelvic irradiation. Results  Five patients underwent laparoscopic ovarian lateral transposition before radiotherapy in order to relocate their ovaries outside the radiation field. A concomitant ovarian wedge resection was performed for ovarian cryopreservation. In two of these women, before dissecting the ovarian cortical tissue for cryopreservation, all visible follicles were aspirated. The sixth patient who had had low anterior resection underwent hormonal ovarian stimulation followed by oocyte retrieval and embryo vitrification. Conclusions  Fertility preservation in women with rectal cancer is feasible. This includes laparoscopic ovarian transposition and cryopreservation of ovarian tissue, embryo, or oocyte.     

化疗对乳腺癌患者骨髓抑制的临床分析

目的：评估化疗后乳腺癌患者发生骨髓抑制的风险。方法：对219例乳腺癌患者化疗前后的部分血液学的指标进行比较,并探讨可能与骨髓抑制相关的危险因素。结果：化疗后患者的WBC、N、HB及PLT数值均下降;与骨髓抑制相关的主要因素有：骨髓转移（OR=2.395,P=0.04）、BMI（OR=0.279,P=0.008）、肿瘤分级（OR=2.876,P〈0.001）及化疗周期（OR=4.639,P=0.006）。结论：根据对骨髓抑制相关因素的评估,临床医生可预测乳腺癌患者发生骨髓抑制风险的大小,从而及时地进行预防或纠正。     

Pregnancy and Breast Cancer: when They Collide

Women of childbearing age experience an increased breast cancer risk associated with a completed pregnancy. For younger women, this increase in breast cancer risk is transient and within a decade after parturition a cross over effect results in an ultimate protective benefit. The post-partum peak of increased risk is greater in women with advanced maternal age. Further, their lifetime risk for developing breast cancer remains elevated for many years, with the cross over to protection occurring decades later or not at all. Breast cancers diagnosed during pregnancy and within a number of years post-partum are termed pregnancy-associated or PABC. Contrary to popular belief, PABC is not a rare disease and could affect up to 40,000 women in 2009. The collision between pregnancy and breast cancer puts women in a fear-invoking paradox of their own health, their pregnancy, and the outcomes for both. We propose two distinct subtypes of PABC: breast cancer diagnosed during pregnancy and breast cancer diagnosed post-partum. This distinction is important because emerging epidemiologic data highlights worsened outcomes specific to post-partum cases. We reported that post-partum breast involution may be responsible for the increased metastatic potential of post-partum PABC. Increased awareness and detection, rationally aggressive treatment, and enhanced understanding of the mechanisms are imperative steps toward improving the prognosis for PABC. If we determine the mechanisms by which involution promotes metastasis of PABC, the post-partum period can be a window of opportunity for intervention strategies.     

乳腺癌幸存者生育意愿量表的修订及信效度检验

目的 修订乳腺癌幸存者生育意愿量表,并进行信度和效度检验。方法 对乳腺癌幸存者生育意愿量表进行跨文化调适形成修订版乳腺癌幸存者生育意愿量表,对308例育龄期乳腺癌幸存者进行调查。结果 修订版乳腺癌幸存者生育意愿量表的总Cronbach′s α系数为0.803,Guttman分半信度为0.731。量表水平的内容效度指数为0.967,条目水平的内容效度指数为0.875~1.000。探索性因子分析提取特征值>1的公因子5个,共解释总变异的76.767%;验证性因子分析显示量表的5个维度对数据的拟合效果较好。与中文版癌症后生育忧虑量表得分的效标效度为0.609。结论 修订版乳腺癌幸存者生育意愿量表具有良好的信效度,可作为育龄期乳腺癌幸存者生育意愿水平的测评工具。     

单核苷酸多态性与乳腺癌化疗应答

目的探讨单核苷酸多态性（SNP）与乳腺癌常规化疗药物治疗应答间的相关性及其在指导个体化治疗中的价值。方法检索Pub-Medline和中国CHKD期刊数据库，对近年来此领域有代表性的文献进行整理、归纳。结果多种药物代谢相关基因存在SNP现象，且与药物效应个体多样性有着密切联系。人种、地域、环境、基因间或药物间相互作用可能会对这种关系产生影响。结论SNP研究对于优化个体用药具有重要的应用前景，但多基因多SNP组合分析以及大样本、前瞻性随机对照研究还非常必要。     

Adjuvant Systemic Therapy of Breast Cancer

The first procedure in primary breast cancer is usually the surgical excision of the tumor. However, a medical therapy is necessary in almost all patients to treat the systemic component of the disease. Which medical approach is recommended depends on the biology of the tumor itself. Endocrine-responsive tumors must be treated by an endocrine therapy according to their menopausal status. In HER2/neu-overexpressing tumors, the monoclonal antibody trastuzumab is part of the standard treatment in combination with chemotherapy. Hormone receptor-negative and non-HER2/neu-overexpressing tumors as well as endocrine-responsive tumors with a high proliferation index or additional risk factors must be treated with chemotherapy as well. This review article gives further information about the available agents and schedules.     

Low Bone Mineral Density in Middle-Aged Breast Cancer Survivors: Prevalence and Associated Factors

BACKGROUND: The aim of this study was to investigate the prevalence of low bone mineral density (BMD) and associated factors in middle-aged breast cancer survivors (BCS). PATIENTS AND METHODS: A cross-sectional study was conducted with 70 BCS of 45-65 years of age undergoing complete oncology treatment. Logistic regression models were used to identify factors associated with low BMD (osteopenia and osteoporosis taken together as a single group). RESULTS: The mean age of participants was 53.2 ± 5.9 years. BMD was low at the femoral neck in 28.6% of patients and at the lumbar spine in 45.7%. Body mass index ≤ 30 kg/m(2) (adjusted odds ratio (OR) 3.43; 95% confidence interval (CI) 1.0-11.3) and postmenopausal status (OR adjusted 20.42; 95% CI 2.0-201.2) were associated with low BMD at the lumbar spine. Femoral neck measurements, age > 50 years (OR 3.41; 95% CI 1.0-11.6), and time since diagnosis > 50 months (OR adjusted 3.34; 95% CI 1.0-11.3) increased the likelihood of low BMD. CONCLUSION: These findings show that low BMD is common in middle-aged BCS. Factors were identified that may affect BMD in BCS and should be considered when implementing strategies to minimize bone loss in middle-aged women with breast cancer.