来源： TOP拓普
美国哈佛大学的Dana-Farber癌症研究所的乳腺癌专家Harold Burstein博士和 Erica Mayer博士最近在做了关于乳腺癌的治疗方法在线答疑活动。这里把一些问题和答案和大家分享。Burstein和Mayer博士是来自Dana-Farber的Susan F. Smith女性癌症中心，乳腺肿瘤中心的乳腺肿瘤内科专家。里面的问题涉及非常广泛，哈佛的两位专家都做了仔细回答，相信无论是患者还是医生，都能从这个问答中获益。
【ER阳性乳腺癌和营养治疗】
Q：我是ER阳性乳腺癌患者，我想知道除了大豆以外还应该避免食用什么食物。同时，对于我来说，除了使用Replens胶以外，还有什么其他方法可以帮助改善由于年老导致的阴道干涩吗？您的建议是什么？
Dr. Mayer:没有可靠的数据表明吃大豆或其他特定的食物会增加癌症的复发风险。一般来说，我们会推荐一些大众健康饮食，即大量的新鲜水果和蔬菜，以及适量瘦肉。
至于阴道干涩，如果非激素阴道润滑液不足以控制症状，可以尝试使用雌激素栓剂或雌激素环来进行局部激素治疗。尽管对于ER阳性乳腺癌患者，我们希望尽量避免雌激素暴露。但是也没有数据表明使用局部激素治疗会增加癌症复发风险。此外，如果阴道干燥症状非常严重，使用局部激素治疗还有助于改善患者生活质量。关于是否适合局部激素治疗，你可以进一步咨询你的医生。
【长春瑞滨和曲妥珠单抗的探索性剂型】
Q：欧洲已经批准了长春瑞滨口服剂和曲妥珠单抗皮下给药。那么，在美国被批准使用的可能性有多大？批准的障碍有什么？
Dr. Mayer:由于目前长春瑞滨口服剂和曲妥珠单抗皮下给药仍在研究中，现在还不清楚它们能否在美国获批，以及什么时候它们能在美国上市。
【关于Faslodex】
Q：我有两个问题。我在辅助治疗时接受了Faslodex。我的肿瘤不是转移性肿瘤，我接受Faslodex治疗的原因是，由于严重副作用或过敏反应，我不能接受任何其他药物治疗。我想知道因为这种原因接受Faslodex治疗的患者有多少？此外，现在我还患上了严重的关节疼痛和炎症，这些症状虽然起病缓慢，但却在不断加重。我讨厌再使用其他药物来治疗关节疼痛和炎症。因为我对许多药物（不只是癌症药物）都产生过过敏反应或副作用。你认为我的关节疼痛和炎症是由于Faslodex导致的吗，我还有什么其他治疗选择吗？
Dr. Mayer:氟维司群（Fulvestrant）不是乳腺癌辅助治疗的常用药物，并且没有临床试验证明氟维司群治疗的疗效如何。如果你产生了新的症状，请咨询你的医生，以讨论进一步的诊断和治疗方案。
【HER2 + IV期乳腺癌， Zometa和Herceptin的治疗疗程】
Q：我在2006年5月被诊断患有HER2 +乳腺癌。在进行乳房肿瘤切除术后，我们发现癌细胞已经转移到肝脏和骨头，所以我在2周内从I期乳腺癌变成了IV期乳腺癌。我接受了几个周期的阿霉素、多西他赛和环磷酰胺治疗，然后进行了肝切除术，术后开始赫赛汀、唑来膦酸、吉西他滨和卡铂治疗。然而，静滴吉西他滨和卡铂治疗后，肿瘤标记物并没有下降。后来我又接受了33轮放疗。现在，我还在接受赫赛汀和择泰治疗。5年来，扫描结果都显示无疾病证据（NED），我的肿瘤标记也几乎正常了。
我的问题是：您觉得我还需要继续接受赫赛汀和择泰治疗吗？有时我觉得我的病情已经控制得很好了，不需要再治疗了。但是同时我也害怕停药后，肿瘤会复发。
Dr. Mayer:恭喜你7年都没有发生癌症复发。关于择泰，长期治疗的疗效是未知的，而且长期治疗可能会导致长期毒性风险。因此你可以考虑停止择泰治疗，或减少至每年两次输注。对于赫赛汀，该药物通常在心脏功能稳定的转移性HER2阳性乳腺癌患者中无限期持续使用。目前，我建议继续使用赫赛汀治疗。
【研究中药物巴多昔芬(bazedoxifene)】
Q：巴多昔芬什么时候可用于治疗转移性乳腺癌？我知道Duke实验室正在进行或已经进行了相关研究。
Dr. Mayer:巴多昔芬是一种骨质疏松症药物，在实验室发现其具有抗乳腺癌细胞的抗癌作用。目前，我们不清楚该药物是否有助于人类乳腺癌治疗，这需要进一步研究。由于其他骨质疏松症药物对乳腺癌的疗效都不确定。所以在试验完成前，我们尚不清楚这种新药物是否有助于人们抵抗癌症。如果你对乳腺癌的新药物感兴趣，请咨询你的医生，看能否参与临床试验。
【临床试验和BRCA1基因突变】
Q：我的问题是关于我姐姐的，她携带有BRCA1基因突变。她的淋巴结已经发生了癌症复发。医生们试图手术切除掉淋巴结，但是淋巴结位置太深，并在动脉附近。化疗可以减小她的肿瘤，但导致了严重的肠道副作用。她进行了二线化疗，也没有效果。三线化疗可能有疗效，但却导致了严重的红斑综合征，并已经停止化疗。现在我姐姐在考虑参加一个试验。我们已经穷尽办法了，你有什么最新的建议吗？
Dr. Mayer:听起来，你姐姐的情况很麻烦。对于对标准化疗耐药的癌症，参加临床试验是一个合理的选择。或者，她可以咨询她的医生，在有BRCA1基因突变乳腺癌治疗经验的中心接受治疗是否会更有帮助。
【芳香化酶抑制剂（Aromasin）的治疗疗程】
Q：我患有发生骨转移的IV期乳腺癌，并通过手术切除了部分肿瘤。过去5年内，我一直在服用芳香化酶抑制剂。但目前我已经发生了脚部神经病变。因此，我担心长期服用芳香化酶抑制剂会导致长期副作用，我想知道我是否可以停止服用这种药物。谢谢。
Dr. Mayer:恭喜你，对于IV期乳腺癌，使用5年的芳香化酶抑制剂（依西美坦）治疗是非常好的！由于您在诊断为转移性乳腺癌后治疗效果良好。一般来说，我们建议继续使用依西美坦治疗。如果发生了副作用，您可以考虑停药一个月，然后再重新服药。这样有时可以有时帮助身体“重启”，并改善症状。
【三阴性乳腺癌的治疗、随访和复发预防】
Q：三阴乳腺癌治疗后的标准护理是什么？我已经完成了肿瘤切除术、化疗和放疗。我是否应该定期进行血液检查、PET扫描等？对于TNBC存活患者，有没有什么药物可以帮助预防肿瘤复发？
Dr. Mayer:对于任何完成治疗的乳腺癌存活者，随访护理包括定期拜访医生。在拜访医生时应进行乳房体检和每年乳房X光检查。对于预后和患者感觉良好的乳腺癌存活者，不需要进行常规血液测试或身体影像学检查。目前，临床试验中有一些新的药物试图治疗三阴性乳腺癌，你可以向你的医生咨询，是否有合适的临床试验可以参加。还有越来越多的数据表明，定期运动和避免体重增加可能有助于改善存活者的预后，特别是对于那些三阴性乳腺癌患者。
【赫赛汀的治疗疗程】
Q：关于赫赛汀长期治疗（+ 6年），您有什么意见？长期来看，对于Her2过表达乳腺癌，还有什么其他治疗选择？
Dr. Mayer:在乳腺癌辅助治疗时，推荐赫赛汀治疗一年。对于转移性乳腺癌患者，只要心脏功能稳定，赫赛汀可以无限期地治疗。目前，对于转移性乳腺癌，没有其他药物有足够数据可以支持其替代长期赫赛汀治疗。
【CYP2D6和他莫昔芬】
Q：我最近完成了乳腺癌相关治疗。我是2a期、2级乳腺癌，Oncotype（肿瘤基因检测）评分17，绝经后，接受了肿瘤切除术和放疗，没有接受化疗。目前，我正在使用他莫昔芬2年治疗，并序贯AI治疗。
1、我没有检测CYP2D6基因多态性以评估我是否可代谢他莫昔芬。我应该接受CYP2D6基因多态性检测吗？有医院对乳腺癌患者常规检测CYP2D6基因多态性吗？
2、如果ER / PR阳性乳腺癌的整体治疗目标是保持低雌激素水平，为什么他们不检测雌激素水平以评估治疗疗效？
Dr. Mayer:目前，关于CYP2D6基因与他莫昔芬治疗疗效的相关性，临床研究的结论还不一致。因此，此时不推荐根据CYP2D6基因检测结果来指导他莫昔芬的治疗。他莫昔芬的作用机制是阻断雌激素，而不是降低雌激素水平，因此检查雌激素水平不能用来评估他莫昔芬的治疗疗效。
【依西美坦和副作用】
Q：依西美坦和心脏问题之间有关联吗？有什么关联？为什么心脏问题会出现在依西美坦的副作用列表中？
Dr. Mayer:依西美坦治疗不会导致明显的心脏病风险。然而，使用芳香酶抑制剂可以增加胆固醇水平和血压。因此，接受依西美坦治疗的妇女应该常规监测胆固醇水平和血压。
【乳腺癌和淋巴瘤】
Q：2007年，我进行了乳房肿瘤切除术以治疗I级浸润性乳腺导管癌。手术之前，我的血细胞计数一直是正常的。但手术后不久，我的血细胞计数开始暴跌。我看到我的肿瘤医生和两个全科医生都说血细胞计数还“不是那么糟糕”，不需要担心。然而，因为健康保险问题，我不得不换了一个医生。我从原来的护理机构拿到了我的病历，并给我的新医生查看。他立即要求我进行一组血液检查，因为我的一个检查结果显示“脾脏明显增大”，这是直到2011年才被诊断发现的。我被告知我有脾边缘区淋巴瘤。我觉得有可能是两次手术使肿瘤细胞转移，才导致淋巴瘤发生的。我的问题是：根据你的经验，我的乳腺癌类型（I级浸润性乳腺导管癌）是否会导致淋巴瘤，或者乳腺癌是否与淋巴瘤相关？
Dr.Burstein：据我所知，乳腺癌和淋巴瘤完全没有关系。我的猜测是，当您在进行乳腺癌诊断的相关血液检查时，在发现血细胞减少之后又碰巧查出了淋巴瘤。
【肝转移】
Q：我在过去4年里一直与乳腺癌做斗争。2011年，肝脏出现了肿瘤转移灶，并在几个月后通过手术切除了肝转移灶。接受阿那曲唑治疗几个月后，又检测到4个新的转移灶。依维莫司+芳香化酶抑制剂对我根本没有疗效。然后，我开始接受希罗达治疗，直到2013年8月，疗效都非常好。我现在在接受紫杉醇治疗。手术或放射治疗是否可以清除肝脏肿瘤转移灶？
Dr.Burstein：一般来说，对于乳腺癌患者，我们不会清除肝转移灶。通常来说，药物治疗是肝转移的标准治疗方法。而手术可能导致患者风险增加，并且大多数情况下，即便进行了手术，术后癌症甚至也会复发。此外，标准放射治疗会对肝脏会造成很大的毒性。一些其他放疗方法可能可以尽量减少副作用，尽管在乳腺癌其他治疗出现同样问题时的解决办法也适用于此。
【紫杉醇】
Q：对于雌激素/孕酮阳性和Her2阴性乳腺癌（例如我），紫杉醇治疗是否可提供额外治疗获益。我目前的治疗方法是AC化疗4个周期后，序贯紫杉醇和激素治疗12周期。并在AC化疗3个周期时（4个周期前），接受消融后放疗。
Dr.Burstein：AC序贯紫杉醇治疗是淋巴结阳性乳腺癌的一种非常标准的化疗方法，特别是对于年轻女性患者、以及高级别乳腺癌患者
【心脏毒性和乳腺癌治疗】
Q：根据我的了解，赫赛汀、AC化疗，甚至芳香化酶抑制剂（AIs）等都可能导致心脏毒性。目前，这一现象已经受到了人们的关注。我调查了2006年时这些治疗的心脏毒性，并因此拒绝接受治疗。现在，对于已经存在心脏问题的部分患者，这些药物的治疗方案有什么改变？对于心脏疾病高危患者，放疗是否也会导致心脏毒性？这些治疗的副作用和死亡率是多少？谢谢。
Dr.Burstein：一方面，这些治疗（曲妥珠单抗，基于蒽环类药物的化疗，AIs和放射治疗）中的任意一种治疗都可能导致心脏损伤。但导致心脏损伤的机制可能不同。曲妥珠单抗（赫赛汀）和AC化疗可损伤心肌，导致心力衰竭。 AIs可导致胆固醇升高和高血压。放疗可导致冠心病加重。
然而，幸运的是，这些治疗导致主要（或甚至更小的）心脏问题的风险非常低。这些治疗中的每一种治疗都是非常重要的乳腺癌治疗手段。对于接受曲妥珠单抗或AC治疗的患者，我们会仔细监测心脏功能。而对于已经存在心脏问题的患者，我们会避免使用这些治疗。因此，尽管这些治疗可以导致心脏损伤，但这是很罕见的。
【异步转移】
Q：对于发生异步转移的患者（转移灶肿瘤标记物与原发性肿瘤不同），目前的治疗方法是什么？
Dr.Burstein：肿瘤标志物通常可用于指导肿瘤治疗。对于雌激素受体（ER）阳性的肿瘤患者，我们将给与抗雌激素治疗。对于HER2阳性乳腺癌，我们将给与抗HER2治疗。
当检查结果不一致时，有时很难知道哪个是“真实的”标记物表达情况。此时，你需要与你的临床团队进一步讨论。
【大豆】
Q：对于雌激素阳性乳腺癌患者，是否可食用含大豆的食物？
Dr.Burstein：绝对没有数据显示，食用大豆会以任何方式影响乳腺癌预后。据悉，在大豆中发现的植物雌激素不具有任何生理效应。如果你喜欢大豆，那就放心享用。如果你不喜欢大豆，那就无需担心。据我所知，在许多食物中经常使用的各种大豆制剂也并不会对乳腺癌患者造成任何影响。
【IV期乳腺癌患者的骨骼健康】
Q：我有IV期乳腺癌，目前在接受择泰（唑来膦酸）治疗。唑来膦酸治疗是否有助于从骨髓中清除癌细胞？
Dr.Burstein：我们对于已经发生骨转移的IV期乳腺癌患者会使用唑来膦酸（Zometa）。它有助于预防骨相关并发症，如骨折或骨痛。
【在他莫昔芬治疗时，药物治疗抑郁症】
Q：在他莫昔芬治疗时，有什么药物被发现有助于治疗乳腺癌后抑郁症？
Dr.Burstein：当女性使用他莫昔芬时，我们应尽量避免使用抗抑郁药安非他酮（Wellbutrin）、百优解（Prozac，盐酸氟西汀）或百可舒（Paxil，帕罗西汀）。因为这些抗抑郁药可能与他莫昔芬有相互作用。郁复伸（Effexor，文拉法辛）是大多数人的良好选择，因为它与他莫昔芬没有药物相互作用。
【夜间盗汗】
Q：你推荐用什么方法治疗夜间盗汗？
Dr.Burstein：随着时间的推移，夜间盗汗有希望会逐渐消失。一些较新的选择性5-羟色胺回收抑制剂(SSRIs)，如文拉法辛，可以减少潮热和盗汗。百优解（Prozac，盐酸氟西汀）或百可舒（Paxil，帕罗西汀）也可以减少这些症状，但它们会干扰他莫昔芬代谢。
【紫杉醇导致的神经病变】
Q：我已经开始发生神经病变（我的肿瘤医生说是由于紫杉醇导致的）。有什么方法可以帮助治疗神经病变吗？
Dr.Burstein：神经病变是紫杉醇化疗的常见副作用。没有众所周知的治疗方法。减少紫杉醇的剂量可以降低神经病变。还有一些消息建议使用谷氨酰胺补充剂，它可能有助于尽量降低神经病变风险。还有人说加巴喷丁（neurontin）可以缓解神经病变症状。
【瑞宁德(Arimidex)的延长治疗疗程】
Q：对于接受了乳房肿瘤切除术和放射治疗的早期乳腺癌患者，瑞宁德(Arimidex)延长治疗5年以上的疗效如何？对于治疗5年后停药的患者，重新开始瑞宁德治疗有什么获益或风险？
Dr.Burstein：没有关于芳香酶抑制剂（AI）治疗超过5年的数据，也没有中断治疗后恢复给药的数据。通常来说，我会告诉我的病人，AI的预计治疗疗程为5年。有数据表明，在他莫昔芬长期治疗的基础上，继续使用他莫昔芬延长治疗，或换成AI治疗是有临床获益的。然而，对于AI长期治疗的患者，我们不知道延长治疗的获益如何。
【饮酒和乳腺癌复发风险】
Q：我听到过关于不增加乳腺癌复发风险的酒精摄入量的不同意见。请问乳腺癌患者是否有必要完全戒酒？在我家，吃饭时饮酒是一种习俗。我希望设置饮酒上限量，而不是完全戒酒。
Dr.Burstein：“所有东西，只要适量就好。有数据表明，过量饮酒（平均每天饮酒超过几杯）从乳腺癌的角度看可能是有复发风险的。事实上，从很多其他观点来看，饮酒可能也是有风险的。话虽如此，偶尔喝一两杯，对乳腺癌存活者并并不会造成真正的影响。
【监测他莫昔芬的疗效】
Q：如果我理解得没错，目前没有办法检测他莫昔芬是否有效，是吗？
Dr. Mayer:的确没有方法可以检测乳腺癌辅助治疗是否“有效”，如他莫昔芬或化疗。我们从数千名妇女的试验中得知，相比接受过时治疗的患者，接受当前推荐治疗的患者预后更好。但是对于个人，我们目前没有方法可以监测癌症治疗的疗效。
【发生副作用时的治疗选择】
Q：我有Her2阳性乳腺癌，手术切除了左侧乳房和11个淋巴结，其中9个是癌性淋巴结。我接受了阿霉素/环磷酰胺，紫杉醇/赫赛汀化疗。然而，当我即将开始赫赛汀单药治疗时，我的肿瘤科医生不得不停止治疗。因为，我的心功能受损了。我接受了PET扫描、乳腺X线照相、乳腺超声等，结果都显示癌症消失了。然而，医生说乳腺癌是一种侵袭性癌症，随时都可能复发。他们在我的肿瘤原发部分开始了放疗。然后，肿瘤医生将决定是否给我使用抗癌药物希罗达（Xeloda）。我的问题是：有没有其他化疗药物，我可以使用，而不会影响我的心脏功能？
Dr. Mayer:通过所有的治疗后，你的预后很好，干得不错！在以赫赛汀为基础的治疗期间，我们会仔细观察心脏，并发现一些女性的心脏功能会下降。幸运的是，赫赛汀导致的心脏功能变化是可逆的，如果停药并使用心脏保护药物，心功能会发生好转。我通常与心脏专科医生（心脏病专家）一起帮助治疗赫赛汀导致的心脏功能变化，如果心脏功能发生改善，我们可以再次小心地启动赫赛汀治疗。
没有任何数据支持在这种情况下使用希罗达（Xeloda）。因此，我也不建议使用希罗达（Xeloda）。我建议尝试继续开始赫塞汀治疗。如果心脏功能还不足以再次开始赫塞汀治疗，我们仍有数据显示，即使只有9周的赫赛汀和化疗联合治疗，也会给患者带来实质性的临床获益。所以请放心，你已经接受了很好的癌症治疗。
【较低剂量的他莫昔芬】
Q：使用低剂量他莫昔芬的风险是什么，如5mg或10 mg，而不是20 mg？我有I期乳腺癌[一个淋巴结中有一个6mm大小的肿瘤]，只有约115磅。他莫昔芬可导致潮热和盗汗，影响了我的生活质量。
Dr. Mayer:在支持使用他莫昔芬作为辅助治疗的试验数据中，每个患者的使用剂量都是每天20mg的标准剂量。我们没有数据表明较低剂量的他莫昔芬治疗可以提供相同的疗效。在考虑使用较低剂量之前，我建议对副作用给予最大程度的支持性治疗，包括使用药物治疗潮热，或者改变服用方式（尝试每天在相反的时间服药；或每次服用10mg，每日两次）。
弗隆（Femara）治疗时出现关节和肌肉疼痛
Q：如何分辨关节/肌肉疼痛是弗隆（Femara）治疗导致的副作用还是肿瘤发生骨转移的症状？
Dr. Mayer:关节僵硬和疼痛是芳香酶抑制剂（AI）的常见副作用，包括弗隆Femara（来曲唑），并且高达一半的使用患者可能出现。如果有人在服用AI时出现这些症状，那么更有可能是药物副作用，而不是复发性癌症。如果症状严重恶化，并且干扰你每天做事情的能力，那么你应该告诉你的医生，并讨论如何处理症状，以及是否需要进一步的治疗。
【治疗疗程】
Q：我是绝经前女性，并在2010年出现小复发病灶后，接受了诺雷得（Zoladex）和瑞宁德（Arimidex）联合治疗（他莫昔芬不适合我）。我的医生没有告诉我治疗的结束日期。那么我应该这样持续联合治疗，直到绝经？我现在43岁，2007年最初诊断为ER /PR +的2A期乳腺癌（2007年进行了化疗、部分乳房肿瘤切除术和放射治疗，2010年进行了乳房全切术）。
Dr. Mayer:你可能需要继续诺雷得（Zoladex）和瑞宁德（Arimidex）联合治疗至少5年（即直到2015年），然后再与医生讨论是否需要进一步的治疗。
【三阴性乳腺癌治疗选择】
Q：我的妹妹是三阴性乳腺癌，BRCA 1基因突变阳性，二氢嘧啶脱氢酶（dpd）缺乏，有2个复发性肿瘤。一个已经被切除，另一个在她的胳膊下。由于这个转移灶太靠近心脏，而且被圆淋巴结包裹，医生无法切除。所有的当前化疗导致她身体状况非常差，由于dpd缺乏，她的肠道功能也受损，还发生了红斑综合征等。现在他们停止了化疗，计划下周尝试放疗。我们还可以考虑什么治疗办法吗？
Dr. Mayer:有许多对三阴性乳腺癌有效的化疗，而且含BRCA1 / 2突变的癌症可能对某些化疗特别敏感。如果她出现某些化疗相关的毒性反应，她可以尝试除此之外的其他化疗药物或减少剂量使用。不同化疗药物毒性反应不同，她可能更能耐受其他化疗药物。此外，目前正在进行大量研究，以探索治疗BRCA1 / 2突变阳性乳腺癌的特殊药物，您的妹妹应该考虑参加相关临床试验。
【地诺塞麦（Xgeva）和择泰（Zometa）】
Q：由于骨转移，我现在在接受地诺塞麦（Xgeva）治疗。地诺塞麦（Xgeva）也是一个治疗骨转移的药物吗，或者我应该使用择泰（Zometa）治疗？
Dr. Mayer:地诺塞麦（Xgeva）和择泰（Zometa）都是被批准用于帮助预防乳腺癌骨转移及相关症状（例如疼痛或骨折风险）的药物。如果地诺塞麦（Xgeva）治疗效果很好，那么不需要换成择泰（Zometa）治疗。
如果您对哈佛大学的肿瘤专家感兴趣，希望和他们交流，可以加【肿瘤资讯】小编的微信：oncologynews
英文原文：
ER-positive breast cancer and nutrition
Q: I am estrogen-positive and am wondering what foods besides soy to avoid. Also, how do I deal with the age-old problem of vaginal dryness and not being able to use anything beside Replens to help. Any suggestions?
Dr. Mayer: There are no firm data that eating soy, or other specific foods, will increase risk of cancer recurrence. In general, we recommend what many consider a healthy diet: plenty of fresh fruits and vegetables, lean meats in moderation.
As for vaginal dryness, if non-hormonal vaginal moisturizers are not adequate to control symptoms, one can try local hormone therapy in the form of estrogen suppositories or rings. Although we do try to avoid hormone exposure after a diagnosis of estrogen receptor positive breast cancer, there are no data that using local hormone therapy will increase risk of recurrence, and these agents can help quality of life if vaginal dryness symptoms are very bothersome. You can discuss your candidacy for these medicines further with your provider.
Investigative forms of vinorelbine and trastuzumab
Q: What is the possibility of the oral form of vinorelbine and the subcutaneous form of trastuzumab being approved for use in the US, as it is in Europe? What are the barriers involved in gaining such approval?
Dr. Mayer: These agents remain under study at this time; it is not clear if or when they will be available in the US.
Faslodex
Q: My question is two-fold. I take Faslodex as my adjuvant therapy. I did not have metastatic cancer; I take it because I was unable to take any other medication due to terrible side effects or allergic reactions. What are the statistics for someone taking it for that reason? Also, I am now having terrible joint pain and inflammation, which started slowly and is progressing. I hate to take other medications on top of this one as I have a terrible history with side effects with lots of medications (not just cancer medications). Do you believe it could come from the Faslodex, and are there any other options out there for me?
Dr. Mayer: Fulvestrant is not a typical agent used as adjuvant therapy for breast cancer, and there is no clinical trial information to describe the percentage benefit to be expected from this therapy. If you are having new symptoms, you should discuss them with your provider for further workup and treatment options.
HER2+ Stage IV breast cancer and duration of therapy with Zometa and Herceptin
Q: I was diagnosed with HER2+ breast cancer in May of 2006, After having a lumpectomy we found out there were mets to the liver and skull, so I went from Stage I to Stage IV in 2 weeks. I did several rounds of Adriamycin, Taxotere and Cytoxan, then had liver resection, started on Herceptin, Zometa, Gemzar and Carboplatin. Dropped Gemzar and Carboplatin as tumor markers weren't dropping. Then had 33 rounds of radiation. I'm still on Herceptin and Zometa. All my scans have been showing NED for 5 years now, and my tumor markers are almost normal.
My question is: What are your opinions on staying on the Herceptin and Zometa? Sometimes I feel like I don't need to be on them any longer as I'm doing so well. But going off them scares me.
Dr. Mayer: Congratulations on doing so well for 7 years! The benefits of long-term treatment with Zometa are not known, and there can be risks of long term toxicity; therefore you could consider either stopping that agent or reducing to twice-a-year infusions. As for Herceptin, this agent is typically continued indefinitely in patients with metastatic HER2-positive breast cancer and stable heart function. I would suggest continuing on Herceptin for the time being.
The investigative drug bazedoxifene
Q: When will bazedoxifene be available for metastatic breast cancer? I know studies are being, or have been, conducted at Duke.
Dr. Mayer: Bazedoxifene is an osteoporosis medication which showed an anti-cancer effect against breast cancer cells in a laboratory experiment. Whether the drug would help treat breast cancer in a human is not known and needs to be studied. The effects of other osteoporosis medications on breast cancer outcomes have been variable, so it is not clear that this new drug will actually be helpful for people until a trial is done. If you are interested in new medications for breast cancer, please speak to your provider about participating in a clinical trial.
Clinical trials and BRCA1 gene mutations
Q: My question is on behalf of my sister, who has the BRCA1 gene. Her cancer returned on a lymph node, which they tried to operate and remove but was too deep and near an artery. Was given chemo to shrink, but had severe bowel problem side effects. Her second line of chemotherapy was not effective, either. Her third chemo may be working but is giving her severe planter syndrome. They have stopped chemo due to this. Considering a trial now. Have you any latest thing you can suggest, as we are at wits end?
Dr. Mayer: This sounds like a difficult situation for your sister. If a cancer is thought to be resistant to standard chemotherapies, consideration of a trial is a reasonable option. Alternatively, she can discuss with her provider if obtaining another opinion on her care at a center that frequently treats women with BRCA1 gene mutations would be helpful.
Duration of Aromasin
Q: I have stage IV breast cancer with mets to bone, which I had partially removed. I have been on Aromasin for the last 5 years. I am worried about long term effects as I am developing neuropathy in my feet and am wondering if I can stop taking this drug. Thank you.
Dr. Mayer: Congratulations on 5 years on Aromasin (exemestane) for Stage 4 breast cancer! As you are doing well with a diagnosis of metastatic breast cancer, in general, we would suggest continuing on the exemestane. If you are experiencing side effects, you could consider taking a month off and then restarting, as sometimes that helps "reset" the body and improves symptoms.
Triple-negative breast cancer treatment, follow up and recurrence prevention
Q: What is the standard of care after treatment for triple-negative breast cancer? Lumpectomy, chemo and radiation were completed. Should there be regular blood tests, PET scans, etc.? Is there any medication that can be given to TNBC survivors to help prevent recurrence?
Dr. Mayer: Following completion of active treatment for any breast cancer survivor, follow-up care includes regular visits with your providers, which should include physical examination and annual mammogram if there is breast tissue. For a breast cancer survivor who is doing well and feeling well, there is no role for routine blood tests or body imaging. There are new agents being evaluated in clinical trials to try to help outcomes in people with triple negative breast cancer, and you can talk to your provider about whether such a trial is available. There are also increasing data that getting regular exercise and avoiding gaining weight may be helpful for survivors, particularly those who have had triple negative breast cancer.
Duration of treatment with Herceptin
Q: What is your medical opinion regarding the long term use of Herceptin (+6 years)? What other options are available for the over expression of Her2 over the long term?
Dr. Mayer: For adjuvant therapy of breast cancer, Herceptin is used for one year. For a patient with metastatic disease, Herceptin is continued indefinitely, as long as cardiac function is stable. There are no other medications with enough data to support their use in place of long-term Herceptin for metastatic disease.
CYP2D6 and tamoxifen
Q: I recently finished treatment for breast cancer. I am Stage 2a Grade 2, Oncotype 17, post menopausal and did a lumpectomy and radiation, with no chemo. I am now on tamoxifen for 2 years to be followed by some AI.
My questions:
1. I was not tested for CYP2D6 to see if I metabolize tamoxifen. Should I be, and do some places do this routinely?
2. If the whole idea of ER/PR-positive breast cancer is to keep the levels of estrogen down, why don't they do tests for estrogen to see if treatment is working?
Dr. Mayer: Trials investigating the relationship between CYP2D6 and outcomes with tamoxifen have not shown consistent results; therefore, at this time CYP2D6 testing to guide decisions about tamoxifen is not recommended. The mechanism of action of tamoxifen is to block estrogen, not decrease levels, therefore checking estrogen levels will not provide a measure of the effectiveness of the agent.
Exemestane and side effects
Q: What is the association, if any, between exemestane and heart problems? Why does this appear in the list of side effects?
Dr. Burstein: There are no dramatic risks of heart disease with exemestane. However, there can be increases in cholesterol and in blood pressure with aromatase inhibitors. Women should get their usual surveillance for those problems.
Breast Cancer and lymphoma
Q: In 2007 I had a lumpectomy for a stage I grade I invasive ductal cell carcinoma. Shortly after the surgery my blood counts, which had been normal all along, began to plummet. I saw my oncologist and two GPs, who all said not to worry, the counts "weren't that bad." However, I had to change doctors because of my health insurance, got my records from my primary care, and went to a new doc. He immediately ordered a panel of blood tests because one of my records showed a "significantly enlarged spleen," which went undiagnosed until 2011. I was told I had splenic marginal zone lymphoma. I feel as if the two surgeries unleashed the lymphoma. My question is: in your experience, does the type of BC I had lead to – or is it somehow connected to – lymphoma?
Dr. Burstein: So far as I know, there is absolutely no relationship between breast cancer and lymphoma. My guess is that the lymphoma was found after the blood count problems as a coincidence when the blood tests were done at the time of your breast cancer diagnosis.
Liver metastasis
Q: I have struggled with breast cancer for the past 4 years. A liver met appeared in 2011; this was surgically removed a few months later. After a couple of more months 4 new mets were detected, under anastrozol therapy. Everolimus + aromasin didn't help at all; I started Xeloda, which went very well until August 2013. I am now on paclitaxel. Is surgery or radiotherapy an option to remove the liver met?
Dr. Burstein: In general, we do not remove liver metastases from breast cancer. Drug therapy is the usual standard approach. Surgery can be associated with substantial risks, and most of the time, the cancer returns even after the surgery. Standard radiation therapy is quite toxic to the liver. There are selective ways of giving radiation that might minimize the side effects, although the same issues about the cancer popping up elsewhere can apply.
Taxol (paclitaxel)
Q: Does treatment with Taxol have added value for women with estrogen/progesterone-positive and Her2-negative tumors, such as mine. Ablation, followed by radiation, at the moment 3 (out of 4) AC chemo's to be followed by 12x Taxol and hormonal therapy.
Dr. Burstein: AC followed by taxol is a very standard chemotherapy treatment for node-positive breast cancers, especially in younger women and especially if the cancer is higher grade.
Cardiac toxicity and breast cancer treatments
Q: From what I have read, it appears that more attention is now given to the possible heart toxicity of such medications as Herceptin, AC chemo and even the AIs. I researched these therapies back in '06 and refused them for that very reason. How are they used differently today, taking into consideration pre-existing heart issues of some patients? Does the same hold true of radiation treatments for those at risk of heart issues? What is the collateral damage and death rate from treatment? Thank you.
Dr. Burstein: On the one hand, each of these treatments (trastuzumab, anthracycline-based chemotherapy, AIs, and radiation therapy) can cause heart damage. The actual kind of heart damage may differ. Trastuzumab (Herceptin) and AC chemo can damage the heart muscle, leading to heart failure. AIs can cause elevated cholesterol and hypertension. Radiation can cause accelerated coronary heart disease.
Fortunately, however, the risk of major (or even minor) heart problems with these treatments is very low. Each of them can be very important parts of a breast cancer treatment program. We monitor heart function carefully in patients getting trastuzumab or AC, and avoid those treatments in women with pre-existing heart problems. As a result, heart damage from these treatments is real, but rare.
Asynchronous metastasis
Q: For patients who develop asynchronous metastasis (tumor markers that differ from the primary tumor), what is the current approach to treatment?
Dr. Burstein: The markers drive the treatment. If the cancer is likely to be estrogen receptor (ER)-positive, we offer anti-estrogen therapies. If it is HER2-positive, we offer anti-HER2 therapies.
It is sometimes hard to know which is the "real" marker profile when there are discordant results. That is a conversation to have with your clinical team.
Soy
Q: What is the present thinking on eating products that contain soy for estrogen-positive breast cancer?
Dr. Burstein: There are absolutely no data that eating soy affects breast cancer one way or the other. The phyto-estrogens that are found in soy are not known to have any physiological effects. If you like soy, enjoy it. If you don't like soy, then don't worry about it. The various soy preparations frequently used in many foods are also not known to have any effects in breast cancer patients.
Bone health in stage IV breast cancer
Q: I have stage IV breast cancer – on zometa – does this help keep the cancer out of my bones?
Dr. Burstein: We use zoledronic acid (Zometa) in stage IV breast cancer that has already spread to the bones. It helps prevent complications in the bones such as fractures or bone pain.
Medications for depression while on tamoxifen
Q: What medications have folks found helpful for depression post-breast cancer and while taking tamoxifen?
Dr. Burstein: When women are on tamoxifen, we try to avoid Wellbutrin, Prozac, or Paxil because of possible drug-drug interactions with tamoxifen. Effexor (venlafaxine) is a good option for many and does not have those drug-drug interactions.
Night sweats
Question: What do you recommend for helping with night sweats?
Dr. Burstein: Hopefully they will fade out over time. Some of the newer SSRIs such as venlafaxine can reduce hot flashes and night sweats. Prozac and Paxil do so, too, but these interfere with tamoxifen metabolism.
Node dissection, snb and axilla radiation
Q: I have Stage IIb breast cancer, invasive ductal carcinoma Grade 1, ER+, PR+, HER2-negative, just finishing neoadjuvant chemotherapy (AC → T), lumpectomy scheduled for December, 3 weeks after last Taxol treatment. I had a lymph node biopsied before diagnosis, metastatic ductal carcinoma. A PET CT showed just this one node hypermetabolic before the start of chemo. Now the node is not palpable and the primary tumor has shrunk considerably, making a lumpectomy recommended. Is it best to have a node dissection, or is it possible to start with a sentinel node biopsy? And what about axilla radiation?
Dr. Burstein: This is a tough one to answer online because the issues are very specific. However, if the node has resolved, we often do the sentinel nodes but not an axillary dissection, and discuss extra radiation fields with the radiation team.
Neuropathy from Taxol
Q: I am starting to experience neuropathy (my oncs say it is from the Taxol). Is there anything that can help with the neuropathy?
Dr. Burstein: Neuropathy is a common side effect related to Taxol chemotherapy. There is no well known treatment for it. Reducing the dose of Taxol can reduce the effect. There are anecdotes to suggest that glutamine supplements may minimize neuropathy, and some people say neurontin reduces the symptoms.
Extending duration of Arimidex
Q: What is the current thinking on extending the length of Arimidex past 5 years after early-stage breast cancer, lumpectomy and radiation or resuming after previously stopping at 5 years and any know benefits/risks?
Dr. Burstein: There are no data for using aromatase inhibitors for durations longer than 5 years, nor for resuming after interruption. I tell my patients to anticipate about 5 years of an AI. There are data that longer durations of treatment built on many years of tamoxifen therapy and then continued tamoxifen or switching to an AI is clinically valuable. However, we don't know if the same rules hold for AI-based therapy.
Alcohol consumption and breast cancer recurrence risk
Q: I've heard differing opinions about acceptable levels of alcohol intake/amounts that may increase risk of recurrence. Is complete abstinence really necessary? Wine with meals is customary in my family. I'd like to set a limit without cutting it out entirely.
Dr. Burstein: "Everything in moderation." There are data that excessive alcohol consumption – average more than a few drinks every day – is probably risky from a breast cancer point of view. It is probably risky from a lot of other points of view, truth be told. Having said that, a drink or two, once in a while, poses no real problems for breast cancer survivors.
Monitoring the effectiveness of tamoxifen
Q: If I understand correctly, there is currently no way to test whether tamoxifen is being effective or not?
Dr. Mayer: There is no testing that we can do to check if an adjuvant therapy like tamoxifen or chemotherapy is "effective." We know from trials of thousands of women that those who pursue recommended contemporary therapies have better outcomes than those receiving older therapies, but for an individual person, we currently do not have a method to check on the status of the therapy against the cancer.
Treatment options when experiencing side effects
Q: I have Her2 breast cancer, had left breast removed and 11 lymph nodes, 9 were cancerous. I did chemo Adriamycin/Cytoxan, Taxol/Herceptin. However, my oncologist had to stop the treatment when I was about to do Herceptin alone. It was affecting my heart. I took PET scan, mammogram, ultrasound, etc., which showed cancer was gone. However, doctor says this is an aggressive form of cancer which can return anytime. They started me on radiation on the area where the cancer erupted. Then the oncologist will decide whether to give me the cancer pill Xeloda. My question is: are there any other chemo drugs that I can use that would not affect my heart?
Dr. Mayer: Good work getting through all of that treatment! We do watch the heart carefully during Herceptin-based therapy, and in some women a drop in heart function is seen. Changes in heart function related to Herceptin can be reversible, and can get better with a break from Herceptin and use of heart medications. I usually work together with heart specialty doctors (cardiologists) to help treat changes in heart function with Herceptin, and if heart function improves, we carefully start the Herceptin again.
Using Xeloda in this situation is not supported by any data and is not recommended; therefore, instead I would suggest trying to get back on Herceptin. If the heart function does not come up enough to try again, we do have data that even just 9 weeks of combination treatment with Herceptin and chemotherapy may provide substantial benefit, so you can feel confident that you have already received excellent therapy for your cancer.
Lower doses of tamoxifen
Q: What are the risks of using a lower dose tamoxifen, i.e., 5 or 10 mg instead of 20 mg? I have stage I breast cancer [one 6mm tumor in one lymph node] and only weigh about 115 lbs. The tamoxifen is affecting my quality of life with hot flashes and night sweats.
Dr. Mayer: The trial data supporting the use of tamoxifen as adjuvant therapy used the standard dose of 20 mg a day in everyone; we do not have data that using a lower dose will provide the same benefits. Before considering a lower dose, I would suggest maximum supportive care for side effects, including use of medications for hot flashes, or changes in how you take the medication (try taking at opposite time of day, or take as 10 mg twice a day) .
Joint and muscle pain while on Femara
Q: How do you know if joint/ muscle pain is a side effect from Femara or a symptom of bone mets?
Dr. Mayer: Joint stiffness and pain are common side effects of aromatase inhibitors, including Femara (letrozole), and can affect up to half of the people taking the medication. If someone is having these symptoms on an AI, it is much more likely to be due to a drug side effect and not recurrent cancer. If symptoms worsen significantly and are interfering with your ability to get things done every day, then you should talk to your doctor about managing these symptoms and whether further workup is necessary.
Duration of treatment
Q: I am premenopausal and have been doing a combo of Zoladex and Arimidex since a very small recurrence in 2010 (Tamoxifen did not work for me). My doctor doesn't give me an end date for this therapy; should I be doing this until menopause? I am 43 and was originally dx with stage 2A ER/PR+ in 2007. (Had chemo, lumpectomy and radiation in 2007; mastectomy in 2010).
Dr. Mayer: You might consider being on the Zoladex and Arimidex for at least 5 years (i.e., until 2015), then discuss with your doctor if further therapy is necessary.
Triple-negative breast cancer treatment options
Q: My sister is triple-negative, BRCA 1, dpd deficient and had 2 recurring tumors. One removed, the other under her arm, which the docs cannot remove, as it is too near her heart and wrapped round lymphs. All chemo's to date making her very ill, bowel affected because of dpd deficiency, and planter syndrome, etc. They have stopped chemo now and trying radiotherapy next week. Is there anything else we should be thinking of?
Dr. Mayer: There are many chemotherapies with activity against triple-negative breast cancer, and cancers with BRCA1/2 mutations may be especially sensitive to certain chemotherapies. If she has had toxicities with some chemotherapies, there should be other options that she could try down the line that have a different toxicity profile and may be more tolerable, or could be used at reduced dose. Also, there is considerable research ongoing now looking into special medicines to treat BRCA1/2-associated breast cancers, and your sister should consider looking into clinical trials.
Xgeva and Zometa
Q: I am on Xgeva for my bones – is that a good drug for this too, or should I be on zometa?
Dr. Mayer: Both Xgeva (denosumab) and Zometa are drugs approved to help prevent problems, such as pain or risk of fracture, related to having breast cancer metastatic to bones. If you are doing well on Xgeva, you do not need to be changed to Zometa.
参考资料：
Dana-Faber Medical Institute. Ask the expert: Q & A on therapies forbreast cancer
http://www.dana-farber.org/Health-Library/Ask-the-expert--Q---A-on-therapies-for-breast-cancer.aspx
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