[CSCO 2017] Dr. Francis， Dr. Peccatori， Dr. Wang and Dr. Yuan’s comments on breast cancer

 

Dr. Wang: Professor Peccatori and Professor Yuan， glad to have this discussion with you on the fertility issues for young breast cancer patients. And first， welcome to Xiamen—a very beautiful coastal city in China. And after CSCO， it’s more? sessions? on breast cancer patients. The medical doctors， professionals in China， are very interested in fertility preservation for young breast cancer patients. So， I want you to share your experience on these issues. The first question is for Professor Francis. I think that reproduction is not only a fair and reasonable demand for women， but， also， a lot to mention in some situations， even for young patients with cancer. And after the completion of standard therapy， many patients are still willing to have a child. Is it safe for young breast cancer patients to get pregnant and are there any potential long-term effects on the prognosis of pregnancy for these young patients?

 

Dr. Francis: So， I think， for young women diagnosed with breast cancer， they really suffer from a double problem. Because firstly， they are dealing with the stress of being diagnosed with the breast cancer. And then， there is the second stress when the doctors talk to them about treatments that might prevent them from having a baby because of early menopause， loss of fertility. And I think this creates a very stressful situation and they are trying to make many decisions in a short period of time. So I think it is very important when a young woman is diagnosed with breast cancer that we try to find out early whether they have completed their child bearing or if they wish to have a future baby or babies， so that we can start planning early. It’s not good enough to—at the last minute， when she sits down to have chemotherapy—say， oh by the way， it could cause menopause. This needs to happen right from the early time that she is going to be having diagnosis and surgery and planning treatment—thinking about the fertility issue. And I think it is definitely reasonable to keep the option of pregnancy， as best as possible， available for these patients. So， I think it’s appropriate for them to consider pregnancy and the multidisciplinary team needs to help with that. So they need support from the surgeon， the medical oncologist， the breast nurse (if they have one) and it should be very early they should be referred for a fertility consultation. So this would be a routine， to offer them this opportunity to have a consultation to see what the options are. We do think it is safe to consider a pregnancy after breast cancer. There is no data that the pregnancy makes the chance of the cancer coming back higher. It is sometimes the case that breast cancer will come back while a woman is pregnant， but we don’t think it’s because she got pregnant.

 

Dr. Wang: So， the pregnancy does not itself increase the risk for these patients?

 

Dr. Francis: No. We don’t believe the pregnancy increases the risk and I think they should have the option—and they should understand that it is an option. I think trying to guide them as to appropriate timing and the overall situation and prognosis—they need our advice about that. But I think we should try to work toward a mutually agreeable plan so that they can have this hope for the future.

 

Dr. Wang: Yes， thank you. And the second question is for Professor Yuan. As we all know， as well as in your lectures this afternoon， treatment of breast cancer now is now a multidisciplinary therapy including surgery， endocrine therapy， chemotherapy， radiotherapy， and targeted therapy. Does this comprehensive therapy affect the pregnancy ability of the young cancer patients? What is your advice for what the Chinese medical doctors should do in their daily practice?

 

Dr. Yuan: A good question. I think that for breast cancer patients， we have several treatments， such as surgery， radiotherapy， chemotherapy， endocrine therapy， the targeted therapy， and so on. And for local regional therapy， that includes surgery and radiotherapy. For these two treatments， I think they do very little harm to the fertility function. But， as for endocrine therapy and chemo， they may do a lot of harm， especially chemotherapy. Several drugs， such as carboplatin， cyclophosphamide， and anthracyclines —these drugs will do harm to the ovarian function. I think in hospitals several years ago—maybe three years ago—we had a survey asking those patients who were younger than 40 years old， how many were willing to have another baby. At that time， 60 percent of the patients said: no， I don’t want another child—because most of them already had one child. We all know that in China， several years ago， we had a one child policy and they already had one child so they said ’no.’ But the world changed. From last year， the policy has opened and the patients could have another child. I think if we have another survey about the same question， maybe the results will be changed. So， the function of the ovaries depends on the treatment and also on the willingness of the patient to want to have a baby.

 

Dr. Wang: Yes， thank you. I think the third question is for Professor Peccatori. And just as we know that many young breast cancer patients are concerned about fertility damage before or during cancer therapy. You gave a very exciting lecture in ESMO just earlier this month and you have much experience in this area. Can you introduce what kinds of strategies we should pay attention to or should be used to protect the patient’s fertility?

 

Dr. Peccatori: I think that first of all—speaking about fertility—it should not be something that should be done just by the gynecologists. I think that the medical oncologists， surgeons， radiation therapists have all the means to address this issue. It’s important to address this issue early at the beginning of the therapeutic pathway because， otherwise， you don’t have the time to do what can be done to preserve the fertility. So it is very important to assess what are the woman’s wishes for subsequent pregnancy after breast cancer from the very beginning. Once you have assessed that， you should also explore if there were any previous gynecological disease that may hamper fertility， if the woman has or has not a partner， and when the pregnancy is planned. Of course， as it has already been said， different treatments have different gonadal toxicity， which varies according to the treatment， but also according to the age of the patient. So that’s another important consideration. Some of the treatments are not per se， gonadal toxic， but may delay the possibility of having a pregnancy. For example， extended endocrine treatment that is so important for improving the prognosis of breast cancer patients whose tumor expresses an endocrine receptor—estrogen and progesterone receptor—of course delays the onset of pregnancy at least 5 to 10 years. So that might be an issue. There are three things that can be done. The first one is to stimulate the ovary and harvest some ocytes—either to freeze the ocytes or fertilize the ocytes and freeze the embryos. This is one possibility. The second possibility， if the patient has to receive chemotherapy， is to give concomitantly to chemotherapy a drug， which is a LHRH analog. There has been a recent met-analysis that describes an almost 15 percent of absolute risk reduction of amenorrhea in women who receive an LHRH analog during chemotherapy. And the third possibility is to discuss with the patient that either within clinical trials (or also outside clinical trials but it’s always better to have clinical trials) the possibility of a temporary suspension of endocrine treatment—if they have to receive endocrine treatment—to look for the pregnancy. And there is a specific trial—the name of the trial is the Positive Trial—which explores the safety of temporary interruption of endocrine treatment and of course the obstetric and neonatal outcomes.

 

Dr. Wang: Thank you for sharing your experience with Chinese medical doctors. I think your experience is helpful for us to understand the safety and appropriate strategies for fertility preservation in young breast cancer patients.

 

Thank you.

 

Dr. Francis: I’m Associate Professor Prudence Francis from the Peter MacCallum Cancer Centre in Melbourne and affiliated with the University of Melbourne. And I do research with the breast cancer trials in Australia and New Zealand and the International Breast Cancer Study Group. And I’m involved in the St. Gallen Panel and the Advanced Breast Cancer Panel， and the SOFT and TEXT trials.

 

Dr. Peccatori: And I am Fedro Peccatori， and I work in Milano at the European Institute of Oncology. I’m also the scientific director of the European School of Oncology， also based in Milano. I’m a medical oncologist and a gynecological oncologist and I’m mainly involved in the treatment of women’s cancer including breast cancer and gynecological malignancy. And my research area is fertility issues in cancer patients.

 

Dr. Yuan: I ’m Yuan Peng from Cancer Hospital， Chinese Academy of Medical Sciences. I’m a medical oncologist， majoring in breast cancer， such as chemotherapy treatment， endocrine therapy， targeted therapy， and other things. Thank you.

 

 

 

王永胜教授：很高兴与各位教授相聚在美丽的海滨城市厦门，在CSCO会议间歇一起讨论年轻乳腺癌患者的生育问题，这也是本次大会上中国专家学者十分感兴趣的话题，希望各位教授可以就此分享经验和看法。首先请教Prudence Francis教授。生育不仅是女性公平合理的要求，即使是罹患乳腺癌的年轻患者。在经过标准治疗后，许多年轻患者仍然希望能完成孕育生命的使命。那么妊娠对年轻乳腺癌患者是安全吗？妊娠对患者的远期生存会造成影响吗?

 

Prudence Francis教授：年轻乳腺癌患者既要面临患病带来的压力，又要承受可能提前绝经、甚至丧失生育能力的负担。越是需要短期内做出治疗决策，越可能加重患者紧张的心理，反而不利于患者的治疗。所以我们需要尽早考虑患者的生育需求问题，比如患者是否已经有子嗣，未来是否有怀孕的意愿等，这样才能尽早的规划治疗方案。显然，如果患者接在受化疗之前才获知其治疗方案可能导致绝经是不妥当的。讨论年轻乳腺癌患者生育问题，需要在早期明确诊断、制定手术等治疗方案时即纳入考虑范畴。尽可能保留患者的生育能力是合理的。外科医生、肿瘤科医生、妇产科医生及专科护士等多学科团队为患者提供尽早的生育咨询应该成为例行程序。我们认为年轻乳腺癌患者在经过规范治疗后进行生育是安全的。目前没有数据表明生育增加乳腺癌复发的风险，少数患者在妊娠期间出现肿瘤复发也并不能归因于妊娠所致。

 

王永胜教授：今天下午袁教授的讲座中提到乳腺癌的治疗应包括手术、内分泌治疗、化疗、放疗和靶向治疗等综合治疗方法。众多的治疗方法是否会影响乳腺癌患者的生育能力？中国临床医生在临床实践中对乳腺癌患者的生育问题需要考虑哪些问题？请袁教授谈谈您的看法。

 

袁芃教授：乳腺癌患者的治疗方法有很多，包括手术、放疗、化疗、内分泌治疗、靶向治疗等。首先，手术、放疗等局部区域治疗对生育功能几乎没有损伤。而化疗等全身治疗对生育功能的损伤相对较大。尤其是铂类、环磷酰胺和蒽环类药物等化疗药造成的卵巢功能损伤是比较显著的。

 

几年前我们医院曾进行了一项调查，询问年龄小于40岁的乳腺癌患者是否希望再生育一个孩子。当时有60％的患者表示没有意愿，因为她们中大多数已经有一个孩子了。这样的结果与当时的中国计划生育政策是分不开的。从去年开始国家已经实行“二胎”政策，逐渐松绑人口计划生育政策。很多育龄女性其实是希望再养育一个孩子的。如果我们再做一次同样的调查可能会得到完全不同的结果。随着经济条件及政策国情等变化，中国乳腺癌患者的生育意愿也会发生变化，临床医生在制定卵巢抑制等内分泌治疗方案时需要及时、充分的考虑患者是否存在生育意愿。

 

王永胜教授：感谢袁教授的回答，接下来我想请教Fedro Peccatori教授。许多年轻的乳腺癌患者在肿瘤治疗开始及治疗过程中都非常关心生育损伤的问题。您在本月初ESMO会议上也做了非常精彩的相关讲座，在年轻乳腺癌患者生育方面有着丰富的经验。请您介绍一下可以采取哪些措施来保护患者的生育能力？

 

Fedro Peccatori教授：首先，保留乳腺癌患者生育能力并不仅仅是妇科医生应该做的，肿瘤科、外科、放疗科的医生都可参与这个问题的讨论。在制定治疗方案的早期即应考虑患者的生育问题，才能提前或有的放矢的实现保护乳腺癌患者的生育功能。临床医生需充分评估患者的情况，如是否存在可能影响生育的妇科疾病、是否有伴侣以及何时计划怀孕等。正如袁教授所说的，不同的治疗方法存在不同程度的生殖毒性，需要考虑患者的肿瘤情况、年龄等客观因素调整治疗方案。另外，一些治疗本身并无性腺毒性，但有延迟受孕的可能，比如延长内分泌治疗可改善激素受体阳性乳腺癌患者的预后，但患者的怀孕计划也需要至少延迟5至10年。如果患者有保留生育功能的意愿，可以考虑以下三种措施来实现：一是刺激卵巢并收获、冻存卵细胞，以备将来行人工辅助生殖；二是必须行化疗的患者可考虑联合应用LHRHa药物治疗，近期的一项荟萃分析显示，化疗联合LHRHa治疗的患者发生闭经的绝对风险率可降低15％；三是目前有一些临床研究，患者可暂停内分泌治疗以获得生育机会，研究过程中会关注患者是否会有肿瘤复发等安全性问题，妊娠及产后全程中观察胎儿及新生儿情况。

 

 

王永胜教授：各位教授讨论了年轻乳腺癌患者的生育问题，主要有以下几个方面内容。

 

第一，我国年轻乳腺癌呈年轻化趋势以及国家放开二胎政策的实施，保留年轻乳腺癌患者生育功能的需求应给予重视。

 

第二，乳腺癌治疗应综合治疗以及多学科团队协作。化疗可导致患者卵巢功能损伤、卵泡数目减少和生育能力降低，不同的化疗方案、持续时间、用药剂量以及不同年龄层患者所发生的卵巢功能损伤程度并不一致；内分泌治疗本身不影响患者的生育能力，但是5至10年的延长内分泌治疗会使患者的生育年龄明显滞后。暂停内分泌治疗对激素受体阳性乳腺癌患者的安全性、预后有何影响？目前的一些回顾性研究显示，患者接受1-2年内分泌治疗暂停治疗并完成生育，在妊娠结束后继续进行内分泌治疗对患者的预后并无不良影响。有些回顾研究显示，由于“健康母亲”效应，完成生育的乳腺癌患者的总体生存和预后优于没有生育的患者。我们期待有更多的前瞻性临床研究能够得到最终结论。

 

第三，在临床实践中如何保护患者的生育能力。三位教授均已提到，在治疗开始之前就应该对有生育能力要求的患者进行充分的沟通和评估，而不是在化疗开始一段时间后再仓促讨论这一问题。现有证据支持胚胎冷冻和卵子冷冻是标准的保护生育能力的方法，而卵巢冷冻和化疗中使用卵巢功能抑制药物也处于研究阶段。在治疗乳腺癌诊断18到24个月以后的妊娠是安全的，不会影响患者的预后。无论患者是否采用胚胎冷冻、卵子冷冻、卵巢冷冻等技术，其化疗过程中短暂使用GnRH-a抑制卵巢功能也是可行的。上述方法均可以保护患者的卵巢功能，保留患者的生育能力。希望通过这些经验分享，有助于国内医生提高保护年轻乳腺癌患者生育能力的意识，以及在临床工作中正确处置这一问题的能力。

 

专家简介

 

王永胜

 

医学博士，研究员，二级教授，博士生导师。山东省肿瘤医院乳腺病中心主任、乳腺癌MDT首席专家，中国抗癌协会乳腺癌专业委员会副主委，中国临床肿瘤学会乳腺癌专家委员会常委，中华医学会肿瘤学分会乳腺癌学组委员，中国医师协会乳腺外科医师委员会常委，国家卫计委乳腺癌诊疗规范专家组成员，GBCC（全球乳腺癌会议）国际指导专家委员会成员。

 

袁芃

 

国家癌症中心、中国医学科学院肿瘤医院主任医师，教授，博士生导师

中国抗癌协会乳腺癌专业委员会秘书长

北京乳腺病防治学会

国际医疗专业委员会主任委员

中国老年学会肿瘤专业委员会常委

中国医药教育协会乳腺疾病专业委员会常委

 

Prudence Francis

 

墨尔本大学彼得·麦卡勒姆癌症中心的副教授。

主要在澳大利亚和新西兰以及国际乳腺癌研究小组进行的乳腺癌临床试验研究工作，St. Gallen共识专家，ABC共识专家，主持SOFT和TEXT试验

 

Fedro Peccatori

 

意大利米兰欧洲肿瘤学院科学主任

医学肿瘤学家，妇科肿瘤学家

主要从事女性肿瘤治疗的相关研究，包括乳腺癌、妇科恶性肿瘤及肿瘤患者的生育问题等