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•简介 •一览表 •症状 •治疗
•饮食习惯的改变 •生活方式的改变 •草药
•营养补充剂 •参考文献
“乳腺癌”是乳腺的恶性肿瘤,在女性中常见而在男性中罕见。它的特征是细胞失去控制、不断分裂形成肿瘤,其中一些细胞可能扩散到其他地方,也称为转移。
对饮食或草药类营养补充剂中提供的某些维生素、矿物质、草药或其它膳食成分是否能降低乳腺癌发生的风险或减轻乳腺癌患者的症状已进行了大量的研究,本文即是对这些研究的讨论和总结。
提供这些信息的唯一目的是为了在消费者和他们的医生讨论有关营养补充剂的问题时有所帮助。我们并不建议,更不提倡、促进、鼓励消费者为了降低癌症风险或治疗癌症而自行购买这些营养补充剂。并且,以下所有信息不应被误解为饮食或草药类营养补充剂能够或应该被用来取代常规的抗癌治疗。
下文提及的某些研究将表明某个特定的饮食成分或饮食、草药类营养补充剂可能对降低乳腺癌风险有效,但是应当注意到它们都仅是初步的证据。还有一些研究表明某个特定的饮食成分在血中的高浓度或饮食中的高水平与乳腺癌风险的降低存在联系。即使该联系被证明确实存在,也不意味着含有大量这一成分的饮食类营养补充剂就一定能起到抗癌效果。
尽管有一小部分女性携带了有害基因因而大大增加了患病风险,但是大多数的乳腺癌都不是遗传性的。家族里有较多乳腺癌患者的女性可以选择向遗传学家(这在很多大医院都可以找到)咨询,看看是否需要进行遗传测试。
绝经后乳腺癌的发病率随地区不同而差异很大,从一个国家迁往另一个国家的女性患上癌症的平均机率,从长期来看会慢慢趋向于与迁入地区一致。这一证据有力地证明了尽管不是全部,但大多数乳腺癌是可以预防的。然而,是哪些因素造成了乳腺癌的发病率出现如此大的差异,将高危人群和低危人群分隔开来,对此人们仍有很大争议。
一些公认的影响患上乳腺癌风险的因素:
• 第一个月经周期出现的年龄越晚,风险越小。
• 在较年轻的时候(十几岁到二十出头之间)发生足月妊娠可降低风险。
• 体重过重回增加绝经后患乳腺癌的风险。
• 使用激素替代疗法会增加患病风险,但已有报道称在停止使用激素后不久,增加的患病风险就会消除。
• 最后一次月经周期时年龄较大(五十出头或更晚)的女性与最后一次月经周期时年龄相对年轻(晚四十岁或者更早)的女性相比会有更高的风险。
还有一些其它的因素可以影响女性患乳腺癌的风险大小。许多研究人员和有些医生相信长期(大于五年)使用口服避孕药会增加绝经前而非绝经后患乳腺癌的风险。同样地,体重过重似乎可以使绝经前患乳腺癌的风险稍减,即便它会增加绝经后患乳腺癌的风险。
几乎所有患有非浸润性乳腺癌(导管内原位癌)和大多数被诊断为淋巴结阴性乳腺癌的女性,都是通过适当的传统疗法治愈的。即使乳腺癌是在扩散到淋巴结之后才被诊断出来,许多病人仍是可以治愈的。一旦乳腺癌已经波及到体内较远的部分,常规疗法就不再能治愈疾病而只能起到延长病人生命的作用。
乳腺癌的辅助疗法
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分级
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营养补充剂
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草药
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次选
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叶酸(可减少饮酒女性的患病风险)
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其它
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辅酶Q10
共轭亚油酸
褪黑激素
维生素D(降低患病风险)
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杂色云芝
刺五加
欧洲槲寄生
绿茶(降低患病风险)
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首选 有可靠和相对一致的科研数据证明其对健康有显著改善。
次选 各有关科研结果相互矛盾、证据不充分或仅能初步表明其可改善健康状况或效果甚微。
其它 对草药来说,仅有传统用法可支持其应用,但尚无或仅有少量科学证据可证明其疗效。F对营养补充剂来说,无科学证据支持和/或效果甚微。
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乳腺癌的症状
乳腺癌的诊断通常是从女性自己或她的医生发现她的一侧乳房有个无痛的肿块开始的。近几年来,乳腺癌的诊断常常在症状还没出现前就从乳房X线常规筛查的可疑发现开始了。在一些发现较晚的病例中,患侧乳房可能出现外形的改变,肿块最终会变得固定不能移动。
如果乳腺癌扩散到体内较远的部分(远处转移),则出现何种症状将取决于癌症已经扩散到哪个部位。例如,如果乳腺癌播散到骨骼,就会造成频繁的骨痛;如果它播散到脑部,通常会引起神经方面的症状,例如服用阿司匹林也不能使之缓解的头痛。当乳腺癌已经波及到体内较远的部分时,它会象其他癌症一样,最终导致体重大幅下降,出现难以治疗的、会使人产生疲劳感的贫血,以及最后无可避免的结局——死亡。
医药治疗
大多数乳腺癌病人都会使用处方药进行治疗,也就是我们常说的化疗,即使这当中许多女性得的是早期癌症(淋巴结阴性乳腺癌)。尽管肿瘤较大的女性患者会在手术前进行化疗,但大多数情况下化疗是从外科手术后开始的。最常用于女性乳腺癌治疗的化疗药包括以下若干药物的组合:环磷酰胺(cyclophosphamide)(Cytoxan®癌得星,Neosar®),氨甲蝶呤(methotrexate)(Folex®,Rheumatrex®),氟尿嘧啶(fluorouracil)(5-氟尿嘧啶(5-FU),Adrucil®,Efudex®,Fluoroplex®),和阿霉素(doxorubicin)((Adriamycin®亚德里亚霉素),Rubex®,Doxil®)。它莫西芬(Tamoxifen),一种抗雌激素(Nolvadex®),用于治疗那些雌激素受体为阳性的乳腺癌病人;其它乳腺癌病人一般不使用它莫西芬进行治疗。有些雌激素受体为阳性的乳腺癌晚期患者还会使用芳香酶抑制剂,以减弱机体产生雌激素的能力。这些药物包括来曲唑(letrozole)(Femara®弗隆)、阿那曲唑(Anastrozole)(Arimidex®瑞宁得)、福美斯坦((Lentaron®兰特隆)、Vorazole(Rizivor®)和依西美坦(exemestane)(Aromasin®阿诺新)。
越来越多的患有非浸润性乳腺癌(导管内原位癌)的女性根据某些危险因素(Van Nuys标准)的大小来确定疾病发展为浸润性(可能威胁到生命的)乳腺癌的危险性,从而在一系列手术和放疗方法中选择治疗方案。小叶原位癌通常并不被认为是乳腺癌,而仅是发生乳腺癌的一个危险因素。大多数患有浸润性乳腺癌的女性最初会被要求从两个治疗方案中选择一个:或者手术切掉肿块(乳房肿瘤切除术)并同时去除腋窝淋巴结,然后进行放疗,或者直接切除乳房(乳房切除术)连同腋窝淋巴结。只在少数病例中,接受乳房切除术的病人会被建议在术后进一步接受放疗。
可能有益的饮食习惯
以下这些饮食上的变化已与乳腺癌进行相关性研究:
戒酒
对各项采用现有最好的方法进行研究的项目进行分析后发现,饮酒女性患乳腺癌的风险比与完全禁酒的女性要高[1]。成年早期的饮酒量与其后年龄稍大时的饮酒量相比更能反映患病风险的大小[2]。
有五项研究[3,4],虽然不是全部[5]但报告说酒精可以提高雌激素水平。雌激素水平的提高可能可以解释患病风险增加的原因。
在一项初步报告中,叶酸摄入量较低的饮酒者与非饮酒者相比,患乳腺癌的风险要高32%;然而,摄入足量叶酸的饮酒者其风险只升高5%[6]。在同一份报告中,补充多种维生素(其中含有叶酸)同时每天喝1.5杯酒的女性与那些饮同样多的酒但是不补充含叶酸在内的多种维生素的女性相比,患乳腺癌的风险要低26%[7]。
纤维
来自谷类的不可溶的纤维可以推迟乳腺癌在动物中的发生[8]。对多项研究得到的数据进行分析表明,食用相对较大量全麸谷类的人患乳腺癌的风险较低[9]。
在一些研究中发现纤维能预防乳腺癌的保护作用在年轻女性中更强[10]。这可能是因为有报道称纤维可以在绝经前妇女中降低雌激素水平,而在绝经后妇女中则没有这一功效[11,12]。然而,另一些研究者报告说纤维似乎能在所有年龄的妇女中达到同样的抗乳腺癌效果[13]。一位知名研究者指出纤维中的活性成分可能是肌醇六磷酸(phytate)和异黄酮(isoflavone),它们即使在不出现雌激素水平没有下降的情况下也能起到保护作用[14]。如果是这些物质起到抗乳腺癌的作用,那么它们在老年妇女和年轻妇女中可能同样有效。
使饮食中的不可溶性纤维含量增加的最好办法是把精米改为糙米,把用白面粉或混合面粉做成的面点类食品改为100%全麦面包、全麦饼干和全谷类薄煎饼粉。精制白面粉通常在食品包装标签上被列为“面粉”、“强化面粉”、“未漂白的面粉”、“硬粒小麦”、“粗粒小麦粉”或者“白面粉”。只含有全麦粉(保存全部营养成分的小麦粉)的面包通常被标为“100%全麦”。
素食主义
与肉食者比较,大多数[15]然而并非所有的[16]研究发现素食者患癌症的可能性较小。研究发现素食者的免疫功能更强大一些,这很可能解释了他们对癌症具有部分免疫力的原因[17]。有报道称素食女性和食肉女性相比雌激素水平更低,很有可能这就解释了为什么素食女性乳腺癌的发病率要低一些[18]。
水果和蔬菜
对17项以乳腺癌风险和饮食为题的研究进行分析,结果表明较高的蔬菜食用量与乳腺癌发病率25%的下降有关[19]。同一份报告分析了12项研究,发现较高的水果食用量与乳腺癌发病率6%的下降有关。然而,当八项规模最大、质量最好的研究的数据被整合后,并未发现水果和/或蔬菜的高摄入量与抗乳腺癌作用相关[20]。因此,水果和蔬菜的食用量对乳腺癌的保护效应仍未得以证实[21]。
番茄
番茄包含番茄红素——一种与β-胡萝卜素结构类似的抗氧化剂。尽管有微量的番茄红素存在于其它的食物中,但从饮食中得到的大部分番茄红素来自番茄。番茄红素已被报道可在体外试管中进行的试验里阻止癌细胞的增殖[22]。
一项对已发表的研究进行的综述回顾发现一共72项研究中有57项支持这一结论:较高的番茄食用量或血中较高的番茄红素浓度与一系列癌症的发病率降低有关。其中35项研究的结果在统计学上有显著意义[23]。番茄的保护作用在一些非乳腺癌的癌症中最为强烈(前列腺癌、肺癌和胃癌),但也有一些证据表明番茄对乳腺癌有一定保护作用。
肉类和它的烹调方法
大多数[24,25]但并非全部[26]研究表明肉的消费量与乳腺癌风险增加有关。这种联系很大程度上取决于肉是如何烹调的。完全熟透的肉比稍稍烹煮过的肉含有更多的致癌物[27]。一些初步研究的证据表明食用完全熟透的肉的女性患乳腺癌的风险较高[28]。遗传因子则决定哪些女性会由于食用完全熟透的肉而增加她们患乳腺癌的风险[29]。
鱼
有报道称吃鱼的人患乳腺癌的风险较低[30]。一些研究者认为鱼中含有的omega-3脂肪酸是鱼可以抗癌的原因所在[31]。
咖啡,与风险无关
有报道称饮用咖啡会增加乳房中非癌性肿块(这类疾病通常被称为乳房纤维囊性化)带来的疼痛感。有研究人员认为乳房纤维囊性化的某些形式会增加患乳腺癌的风险[32]。正入上述这些相互独立的研究结果所提示的那样,一些女性可能会担心饮用咖啡会增加患乳腺癌的风险。然而,大多数研究已经表明饮用咖啡的女性不比那些不饮用咖啡的患乳腺癌的风险更高[33,34,35]。
橄榄油
在一些初步的研究报告中指出橄榄油的消费与乳腺癌风险的下降有关[36,37,38]。在橄榄油中发现的主要脂肪酸是油酸,但它似乎并不是这一保护作用的原因[39]。科学家们现在猜测橄榄油中存在着一些尚未被发现的物质可能解释橄榄油所具有的保护作用[40]。
膳食脂肪的双面性
橄榄油和鱼被认为是膳食脂肪中对乳腺癌可能有保护作用的两个来源[41,42,43,44] 。两者都分别在上文中讨论过了。以下讨论一些研究者们担心有可能会增加癌症风险的膳食脂肪来源。
高脂肪的饮食会在动物中增加患乳腺癌的风险[45]。女性患乳腺癌的风险在各国不同,但与各国的饮食中总的脂肪消费量成正比关系[46]。有报道称雌激素水平、体重和乳腺密度在女性低脂饮食时都会下降——这些变化都被认为可以降低患乳腺癌的风险[47,48,48,49,50]。并且,有报道称乳腺癌患者的膳食中如果含有大量饱和脂肪酸会降低她们的生存率[51]。(大多数情况下饱和脂肪酸存在于肉类和奶制品的脂肪中。)类似地,已有报道称如果乳腺癌病人食用更多的高脂肪食品,例如黄油、人造黄油、红肉和腌熏猎肉,则癌症的复发率会上升[52]。
对根据受试者记忆而设计的人类试验进行分析,结果同样表明高脂饮食的女性患乳腺癌的风险更高[53]。在某些案例中,这种关联十分紧密[54]。然而,大多数[55,56,57]但不是所有的[58]“前瞻性”研究——可避免由于错误的记忆而带来的误差——并未发现脂肪摄入量和乳腺癌之间有关联。
为什么有些研究成果表明脂肪会增加癌症风险而其他研究则并未发现两者有关?一些发现膳食脂肪和癌症风险无关的研究并没有把橄榄油或鱼的脂肪在其中的作用除外考虑;但两者实际上都有抗癌作用[59,60,61,62]。而把它们算在膳食脂肪总摄入量内再来研究是不是“脂肪摄入量增加使癌症风险增加”显然是错误的。一些发现脂肪摄入量和乳腺癌风险无关的研究同时犯了上述两个错误或其中之一[63,64]。
科学家们知道如果癌症是由膳食不当造成的,则很可能要等引发癌症的食物被规律食用许多年后才会出现癌症。一组研究人员把十年前的膳食摄入和十年后的癌症发生率相比较,并排除了鱼类脂肪的影响后,发现动物性脂肪(除了鱼以外)的摄入量和五十岁以上女性因乳腺癌而死亡的风险有很高的相关性[65]。
在膳食脂肪会否增加乳腺癌风险的争论中,在一个事实是无可争辩的:肉类和奶制品脂肪消耗量较高的国家女性患乳腺癌的风险较高,而那些主要食用谷类、大豆、蔬菜和鱼(而不是肉类和奶制品脂肪)的国家女性患乳腺癌的风险较小[66]。
大豆食用量和乳腺癌风险之间的复杂关系
在大豆消费量较高的亚洲国家中乳腺癌发病率通常较低。然而,这些国家的饮食习惯与那些高危国家的有很大不同,以至于仅仅根据这一证据就把抗乳腺癌的作用单独归结为是大豆的功劳未免过于草率[67]。类似地,有报道称在同一社会范围内,经常食用豆腐的女性患乳腺癌的风险较低[68]。豆腐的食用可能仅仅是对其他可以抗乳腺癌的饮食习惯或生活方式的一个标记。
染料木黄酮(Genistein),一个可以在许多豆制品中发现的异黄酮物质,在体外试管研究中可以抑制乳腺癌细胞的增殖。大多数针对动物的研究报道说大豆和大豆异黄酮可以预防乳腺癌[69]。然而,在动物中发现的保护效应主要是在青春期前饲喂大豆时观察到的[70]。如果在人身上同样如此,那么在成人期食用豆制品可能就几乎起不到什么预防乳腺癌的保护作用。
近来的几个研究结果表明食用大量大豆也许,在某些情况下,会增加患乳腺癌的风险[71,72,73,74,75]。当动物的卵巢被切除后——与行全子宫切除术后的女性情况类似——饮食中的染料木黄酮被报道可以促进乳腺癌细胞的增殖[76]。有报道称给怀孕的大鼠注射染料木黄酮后,她们的雌性后代患乳腺癌的风险会增加[77]。虽然绝经前女性在食用大豆后会表现出雌激素水平下降[78,79],但也有报道会出现前雌激素(proestrogenic)效应[80]。绝经前女性服用大豆异黄酮会增加乳腺分泌——该结果被认为可以增加患乳腺癌的风险[81]。在另一个的试验中,从之前给予含有异黄酮的大豆营养补充剂的女性身上得到的健康乳房细胞会表现出增殖速率增加的现象——这也可能会增加乳腺癌的风险[82]。
因此在人们脑海中普遍存在的观念——食用大豆或者异黄酮如染料木黄酮可以预防乳腺癌的想法还远未得到证实[83,84,85,86,87]。也许在童年时期食用大豆最终会被证明具有一定保护效应[88]。而在成人期做同样的事,则会有截然相反的效果[89,90,91,92,93]。
有些科学家仍对食用大豆至少在某些情况下可以预防乳腺癌抱有希望。这些科学家推荐食用由大豆做成的食物(比如豆腐),而反对用异黄酮营养补充剂。除异黄酮外在大豆中还有几种物质在初步研究中显示出了抗癌活性[94]。
减少糖的摄入
有初步研究报道糖或含糖食物的摄入量增加与乳腺癌风险增加有关[95],尽管这方面的研究结果在已发表的各项研究中并不一致[96]。即使该联系确实存在的话,到底是因为糖可以直接促进癌症发展还是糖的摄入量仅仅是其它的饮食习惯或生活方式因素的标记,还属未知。
可能有益的生活方式
以下这些生活方式的改变进行了与乳腺癌的相关性研究。
运动和预防
已有报道称少女时期大量运动会使成年时患乳腺癌的风险下降[97]。虽然有些医生推测在青春期前锻炼的少女可能是由于减少了月经周期的次数,降低了对雌激素的暴露程度,因而最终使乳腺癌风险降低,但这些效果可能只在那些运动很剧烈的女孩身上出现[98]。
大多数[99,100]然而并非有的[101]研究发现时常锻炼的成年女性较少得乳腺癌。有报道称参加锻炼的女性比那些不活跃的女性出现乳房Ⅹ线摄片的高危图像的危险性要小[102]。
在成人期锻炼可能是通过降低血液中雌激素的水平或者帮助控制理想的体重来预防乳腺癌发生。除运动带来的预防效果外,已有报道称有氧运动可以减轻已被诊断为患有乳腺癌的女性患者的抑郁和焦虑[103]。
吸烟和风险
有些研究发现吸烟和患乳腺癌风险增加有关,这其中包括二手烟的影响[104]。然而,有些报告并未发现这两者有关[105]或发现吸烟似乎与预防乳腺癌发生有关[106]。报告吸烟有害的一些研究发现童年时期暴露于香烟的烟雾下似乎很可能会增加患乳腺癌的风险[107]。
精神-躯体关系
有些研究指出在确诊为乳腺癌前的数年里曾经历过严重抑郁(较轻的不算)的女性患乳腺癌的风险会增加[108]。有些[109,110]然而并非所有的[111]研究发现严重的压力事件可以增加女性患乳腺癌的几率。在一项研究中,经历严重压力事件(如配偶死亡或离婚)的乳腺癌病人,与未遭受这些压力事件的女性相比其复发的风险要高出五倍以上[112]。虽然压力长期以来就被认为可能是一个危险因素,但有些研究并未在心理应激源和乳腺癌发生风险[113]或复发风险[114]之间发现明显关联。类似地,已有报道称心理上的痛苦感受(独立于外在的应激源而存在)与乳腺癌存活率的下降或其复发风险没有关联[115]。
已有报道称心理应激会削弱乳腺癌病人的免疫系统[116]。有报道称良好的社会支持可加强乳腺癌病人的免疫功能[117]。这些发现说明精神因素可能通过某种途径影响乳腺癌复发几率[118,119]。
一项研究发现在手术后数个月内有良好社会支持的乳腺癌病人与那些无人倾心交谈的病人相比,七年内死于乳腺癌的风险仅是后者的一半[120]。10年[121]和15年后,[122]态度无助无望或者持斯多葛派信条(淡泊主义)的乳腺癌病人与研究者称之为具有“战斗精神”的女性相比,其生存可能性要小很多。在一项长达五年的研究中发现无助/无望态度与乳腺癌病人复发或死亡风险增加有关,但是“战斗精神”并没有表现出防止复发或死亡的特殊保护作用[123]。一项临床试验报告说对无助/无望的乳腺癌病人提供仅仅八星期的心理治疗就能改变她们的生活态度,减轻心理痛苦[124]。
若干使用各种心理干预治疗方法的临床试验报告说接受心理咨询或者精神疗法的女性与没有受到心理干预的女性相比,寿命要长[125]——即使在患有晚期癌症的女性中也一样[126]。在一项现在很有名的试验中,全年进行、每周90分钟的援助小组使这些晚期乳腺癌病人的存活寿命提高,平均起来是没有这样的心理支持的类似患者的两倍长[127]。
最后,有报道称放松训练可以减少乳腺癌病人在心理上的痛苦[128],小组疗法和催眠可以减轻晚期乳腺癌病人的疼痛[129]。
即使广泛的心理支持(每周同伴支持、家庭疗法、个别咨询和使用正面的心理意象)都不能在所有的研究项目中使乳腺癌存活率有明显的提升。[130]为什么有些研究可以发现明确的与乳腺癌患病、复发或生存有关的精神-躯体联系,而其它研究中则没有发现这样的联系呢,这仍属未知。
体重超重和风险
体重过重会增加绝经后患乳腺癌的风险,这是一个被研究者们广泛接受的事实。体重过重并不会增加绝经前患乳腺癌的风险,甚至在年轻女性中还可能使患乳腺癌的风险稍稍下降[131]。
可能有益的营养补充剂
以下各营养补充剂与乳腺癌的关系已经过研究。
叶酸
有初步研究表明那些在饮食中补充相对大量叶酸的饮酒女性患乳腺癌的风险要低于那些同样饮酒但是摄入叶酸偏少的女性[132]。在一份类似的报告中,服用含有叶酸的营养补充剂与这些饮酒女性中乳腺癌风险较低有关,同样饮酒但是不服用这些营养补充剂的女性则患病风险较高[133]。
酒精对DNA(细胞正常复制需要依靠该物质)的破坏作用可被叶酸部分抵销。因此,饮食中的叶酸、叶酸营养补充剂和在饮酒女性中预防乳腺癌的作用之间可能存在联系,并且这些联系与我们对于这些物质的生化效应的理解是一致的。与那些饮酒量相同但是没有摄取含叶酸的营养补充剂的女性相比,如果每天一共从食物和营养补充剂中至少摄取600微克叶酸,可在每天喝1.5杯酒以上的女性中把乳腺癌发病率降低43%[134]。
目前还没有研究探索过叶酸营养补充剂在已被诊断患有癌症的女性中的效果。正在服用化疗药物甲氨蝶呤的癌症病人不得在未经肿瘤专科医生指导的情况下服用叶酸营养补充剂。
硒
血中高水平的硒和男性中癌症低发率的关系相当稳定[135,136,137]。然而,大多数[138,139,140,141]虽然不是所有的[142]研究发现硒与女性患上癌症的风险无关,尤其是在那些只发生于女性的癌症。实际上,有些研究报道说暴露于更多量的硒[143]——包括来自营养补充剂的硒[144]——与女性中几种癌症的高发有关,尽管这些研究已遭到了批评[145]。
一个著名的双盲试验曾报告硒营养补充剂可以使肺癌、结肠癌和前列腺癌的发病率大幅下降,在这个试验中有些女性患上了乳腺癌,其中服用硒的人数比服用安慰剂的要多,但这些差异很有可能是由误差造成的[146]。这样,该著名试验的结果也不能支持用硒营养补充剂预防乳腺癌的想法[147]。
相反,动物研究常常发现硒能帮助预防乳腺癌[148,149],高水平的硒和女性患乳腺癌的风险降低之间的关系也时有报道[150,151]。除外这些令人鼓舞的结果,大多数研究表明体内高水平的硒对预防乳腺癌没有什么作用[152,153,154,155,156,157,158]。
维生素E
虽然有些初步的证据表明维生素E可以预防乳腺癌[159,160],大多数研究并不支持这一结论[161,162,163]。在一项初步的研究中,服用维生素E营养补充剂的女性与其它女性患乳腺癌的风险一样高[164]。然而,在某项研究中,血中硒和维生素E水平都低的女性与两种营养成分水平都高的女性相比,患乳腺癌风险要高出十倍[165]。虽然维生素E和硒在身体共同发挥作用,但该项发现的意义并不十分清楚;大多数对维生素E或者硒的效果分别进行研究的项目表明两者对乳腺癌都不起保护作用。
虽然维生素E的一个形式——α琥珀酸生育酚(alpha tocopheryl succinate)——已经被鼓吹为可能是治疗女性乳腺癌的新疗法,但目前仅在体外试验中证明它有抗癌活性[166],尚未在乳腺癌病人中进行任何临床试验。
维生素D
有报道称乳腺癌发病率在阳光照射量低的地区相对较高[167]。阳光可促进维生素D在皮肤的合成,然后它在肝和肾中被活化为一种活性较高的激素。这些活化型的维生素D会造成“细胞分化”——一种本质上和癌症相反的活动。
以下证据指出维生素D可能对乳腺癌有预防作用:
-人工合成的维生素D类似物可阻止动物中与乳腺癌相对应的疾病的发生[168]。
-激活后的维生素D似乎有抗雌激素的活性[169]。
-日光照射和饮食中维生素D的含量都与乳腺癌风险下降有关[170]。
活化维生素D
活化维生素D有几种形式。其中一个——1,25-二羟骨化醇(dihydroxycholecalciferol)——完全就是人体中合成的激素的翻版。
以下各初步的、非临床的证据支持活化维生素D可能对某些乳腺癌病人有所帮助:
-一个人工合成的、与活化维生素D类似的分子与它莫西芬联合应用时在体外试验中使试管中的乳腺癌细胞生长受到抑制[171]。
-人工合成的维生素D类似物可诱导乳腺癌中肿瘤细胞的死亡[172]。
-活化维生素D可抑制移植入动物的人类癌细胞的生长[173]。
-在体外试管中的研究结果表明,活化维生素D可以增强化疗的抗癌效果[174]。
在一项初步临床试验中,每天一次连续六个星期将活化维生素D局部涂抹在乳房上。参加试验的共有19位乳腺癌患者[175]。在完成试验的14个患者中有3个人的肿瘤明显缩小了,还有一位患者也表现出轻度改善。对治疗有反应的患者的肿瘤中有活化维生素D的受体。然而,其它初步性报告并未发现这些受体的高水平总能与较好的预后相关[176,177,178]。
医生开出处方后,负责配药的药剂师就可以把活化维生素D(一种激素)混入用于局部治疗的油膏中。由于该激素具有潜在的毒性,即使只是局部应用,也要求医生对其仔细进行监测。标准的维生素D营养补充剂不太可能像活化维生素D那样在女性乳腺癌患者中产生有同样的效果。在前面提到的那个乳腺癌试验中所有患者都在局部有晚期肿瘤。
褪黑激素
有报道称褪黑激素在大多数[179,180]虽然不是所有的[181]试管内研究中表现出抗乳腺癌细胞的活性。在一项初步的临床试验中,作为受试者的乳腺癌病人之前采用它莫西芬治疗时并无效果或仅有一时的作用[182]。在试验过程中,这些女性再次被给予它莫西芬,但这次是和褪黑激素一起服用。结果血中IGF-1(乳腺癌恶化的标志)的浓度明显下降。有证据表明在这十四个病人中,其中四个病人的肿瘤缩小了,并且这一效果平均保持了八个月长的时间。
大多数研究褪黑激素效果的癌症临床试验的用量为每24小时20毫克,都在临睡前服用[183,184,185,186,187,188,189,190,191,192,193,194]。任何人都必须在专业的医疗人员监督下才能使用这样高剂量的激素。
辅酶Q10(CoQ10)
法国研究人员报道说乳腺癌病人血中辅酶Q10的浓度越低,则病人复发的机会就越大[195]。近几年来,丹麦和美国的研究人员正在研究辅酶Q10在32位乳腺癌病人中使用的效果,这些病人或是癌症复发几率非常高,或是已被诊断为晚期癌症[196]。18个月后,仅有一个病人复发,其他所有人都仍然活着,那些临床试验开始时还不是晚期的病人也没有进一步发展为晚期癌症,开始是晚期癌症的一位病人病情得以控制,还有两位晚期癌症病人的情况大大好转了[197]。在服用营养补充剂两年后病人的情况仍然比较好[198],三到五年以后,在临床试验开始时还患有晚期癌症的病人出现了惊人的好转[199]。
一开始辅酶Q10的剂量是每天90毫克。在后来的报告中,辅酶Q10的剂量增加了,有些女性甚至每天服用390毫克[200]。开始时辅酶Q10是和许多其它营养补充剂一起使用的[201]。但该临床试验的研究人员把观察到的疗效主要归功于辅酶Q10的作用,因而在随后的报告中就再未提及又使用过其它的营养补充剂了[202,203,204]。
这项初步的研究在实施时并没有设置对照组,在发表的论文中也仅就大多数受试者的情况做了粗略的说明。其中一些病人在服用辅酶Q10时还在接受常规治疗。因此,辅酶Q10能否作为癌症治疗的手段仍未有定论。
纤维
虽然我们也能通过营养补充剂的形式摄取纤维(比如Metamucil®),但纤维摄入量的大部分是来自食品的。有初步证据表明大量摄入纤维可以减少患乳腺癌的风险。参见上文饮食习惯改变部分中有关纤维及其可能具有预防乳腺癌作用的讨论。
吲哚-3-原醇
十字花科的蔬菜——花椰菜、抱子甘蓝、花菜和卷心菜——含有一种称为吲哚-3-原醇的物质(I3C)。根据初步的研究,已有报道称I3C可以通过某种途径影响雌激素的代谢,因而可用来预防乳腺癌[205],动物实验[206]和体外研究都支持这一说法[207]。目前为止还没有任何临床试验研究过I3C营养补充剂在女性乳腺癌患者中使用的效果如何。
二吲哚甲烷(Diindolylmethane)
二吲哚甲烷也是在十字花科蔬菜中发现的。体外试验[208]和动物实验[209]表明它可以帮助预防乳腺癌。然而,目前为止还没有二吲哚甲烷在癌症病人中应用的临床试验发表。
葡萄糖酸钙(Calcium D-glucarate,D-葡萄糖二酸(D-glucaric acid))
有作为营养补充剂的葡萄糖酸钙,但也能在水果和蔬菜中找到与它稍有不同的形式——D-葡萄糖二酸(D-glucaric acid)[210]。有初步证据表明葡萄糖酸钙可以间接帮助身体降低雌激素负担,从而降低患乳腺癌的风险[211]。虽然动物研究支持这一可能性,[212]但还没有评估D-葡萄糖二酸营养补充剂是否对乳腺癌的有治疗或预防效果的人体临床试验以论文发表。
IP-6
Ip-6(也叫肌醇六磷酸(inositol hexaphosphate)、植酸(phytate或者phytic acid))可在许多食物中找到,尤其是燕麦麸皮、小麦麸皮和未经发酵的(平)面包。直到最近,大多数IP-6研究都把主要精力放在IP-6的副作用上——干扰矿物质吸收。然而最近的一些动物实验发现IP-6有抗癌活性[213]。但还没有评估IP-6营养补充剂是否对乳腺癌有治疗或预防效果的人体临床试验以论文发表。
大豆异黄酮,包括染料木黄酮
目前还没有研究去探索大豆异黄酮营养补充剂是否能预防乳腺癌或者帮助治疗患有该疾病的病人。尽管如此,已有大量初步的资料说明大豆异黄酮和乳腺癌之间有关。如需获得更多信息,请见上文饮食习惯改变部分中关于大豆的讨论。
共扼油酸(CLA)
初步的动物试验和体外研究说明CLA可以降低数个部位的癌症发生率,包括乳房、前列腺、结直肠、肺、皮肤和胃[214,215,216,217]。但CLA是否在人体中也有类似保护效应仍有待研究。
有无副作用及药物之间相互作用?
请参考各种营养补充剂的副作用及药物相互作用。
可能有益的草药
以下各种草药与乳腺癌的关系已得到研究。
大蒜和洋葱
对大蒜(Allium sativum)和洋葱(Allium cepa)的食用量和乳腺癌风险降低之间的关系进行了初步研究但得到的结果并不一致[218,219];因此,没有证据说明这两种食品可以帮助预防乳腺癌。
云芝(Coriolus versicolor)
有报道说云芝(中国产的一种真菌)可以改善免疫功能[220]。日本人从这种植物中提取出一种称为云芝孢内多糖(Polysaccharide Krestin,PSK)的物质,已在许多临床试验中与常规疗法一起应用于癌症病人[221,222,223,224,225,226,227,228,229]。PSK在女性乳腺癌患者中应用的效果却并不一致。一个双盲临床试验报告说有些组的女性乳腺癌患者在PSK和化疗一起应用时比那些只进行化学治疗的效果要好[230]。另一个双盲试验报告说PSK和化疗一起应用的乳腺癌病人存活率为81%,而只进行化疗的存活率只有65%,但是这些差异没有统计学上的显著意义[231]。还有一个双盲试验没有发现PSK对女性乳腺癌患者有益[232]。
PSK在美国还未上市,在日本也需要有处方才能拿到。尽管用热水从云芝中提取的产物在美国无需处方就能买到,但这种产品是否与日本PSK具有同样的效果就不清楚了。
刺五加(eleutherococcus senticosus,Acanthopanax s.)
刺五加又称为西伯利亚参(Siberian ginseng),在俄国临床试验中已在癌症病人尤其是乳腺癌病人身上得到应用,初步研究结果表明它可以增强人体免疫力[233,234]。这些临床试验所用的剂量通常是一天三次,每次1到2ml液体提取物,至少服用一个月。这些临床试验中的大多数患者同时接受化疗、放疗和/或外科手术[235,236]。在某些俄国临床试验中发现同时服用刺五加提取物的人在接受常规治疗时表现出更小的副作用。并无研究提及刺五加能否预防癌症,也没有临床试验探索刺五加提取物是否影响女性乳腺癌患者的复发或者存活率。
欧洲槲寄生(Viscum album)
在几项针对癌症病人的阳性/阴性双盲试验中将欧洲槲寄生的特别提取物进行皮下注射[237,238,239,240,241]。一项针对女性乳腺癌患者(都接受化疗)的双盲试验发现那些接受槲寄生注射的患者与那些接受安慰剂的相比,免疫力和生活品质都有所提高[242]。还未在乳腺癌病人中研究过槲寄生口服制剂的效果。槲寄生针剂(通常这种产品称为Iscador®)仅能通过医生处方拿到,并且在美国还未上市。不知道美国槲寄生(Phoradendron leucarpum)是否具有和欧洲槲寄生一样的效果。
绿茶
在一项日本研究中,绿茶的消费量和患有早期乳腺癌女性生存时间的增加和肿瘤向淋巴结扩散的减少有关,但和晚期乳腺癌病人的好转无关[243]。研究发现每天至少喝五杯绿茶的患者复发率最低[244]。然而除去上述这些研究外,没有证据显示绿茶对乳腺癌病人有益或者能帮助健康女性预防乳腺癌。
有无副作用及药物之间相互作用?
请参考各种营养补充剂的副作用及药物相互作用。
参考文献
1. Smith-Warner SA, Spiegelman D, Yaun SS, et al. Alcohol and breast cancer in women. A pooled analysis of cohort studies. JAMA 1998;279:535–40.
2. Garland M, Hunter DJ, Colditz GA, et al. Alcohol consumption in relation to breast cancer risk in a cohort of United States women 25–42 years of age. Cancer Epidemiol Biomarkers Prev 1999;8:1017–21.
3. Purohit V. Moderate alcohol consumption and estrogen levels in postmenopausal women: a review. Alcohol Clin Exp Res 1998;22:994–7.
4. Ginsburg ES, Mello NK, Mendelson JH, et al. Effects of alcohol ingestion on estrogens in postmenopausal women. JAMA 1996;276:1747–51.
5. Becker U, Gluud C, Bennet P, et al. Effect of alcohol and glucose infusion on pituitary-gonadal hormones in normal females. Drug Alcohol Depend 1988;22:141–9.
6. Zhang S, Hunter DJ, Hankinson SE, et al. A prospective study of folate intake and the risk of breast cancer. JAMA 1999;281:1632–7.
7. Zhang S, Hunter DJ, Hankinson SE, et al. A prospective study of folate intake and the risk of breast cancer. JAMA 1999;281:1632–7.
8. Rao GN, Ney E, Herbert RA. Influence of diet on mammary cancer in transgenic mice bearing an oncogene expressed in mammary tissue. Breast Cancer Res Treat 1997;45:149–58.
9. Jacobs DR Jr, Marquart L, Salvin J, Kushi LH. Whole-grain intake and cancer: an expanded review and meta-analysis. Nutr Cancer 1998;30:85–96.
10. La Vecchia C, Ferraroni M, Franceschi S, et al. Fibers and breast cancer risk. Nutr Cancer 1997;28:264–9.
11. Golden BR, Woods MN, Spiegelman DL, et al. The effect of dietary fat and fiber on serum estrogen concentrations in premenopausal women under controlled dietary conditions. Cancer 1994;74(3 Suppl):1125–31.
12. Stark AH, Switzer BR, Atwood JR, et al. Estrogen profiles in postmenopausal African-American women in a wheat bran fiber intervention study. Nutr Cancer 1998;31:138–42.
13. Baghurst PA, Rohan TE. High-fiber diets and reduced risk of breast cancer. Int J Cancer 1994;56:173–6.
14. Cohen LA. Dietary fiber and breast cancer. Anticancer Res 1999;19:3685–8.
15. Frentzel-Beyme R, Chang-Claude J. Vegetarian diets and colon cancer: the German experience. Am J Clin Nutr 1994;59(suppl):1143–52S.
16. Kinlen LJ, Hermon C, Smith PG. A proportionate study of cancer mortality among members of a vegetarian society. Br J Cancer 1983;48:355–61.
17. Malter M, Schriever G, Eilber U. Natural killer cells, vitamins, and other blood components of vegetarian and omnivorous men. Nutr Cancer 1989;32:271–8.
18. Armstrong BK, Brown JB, Clarke HT, et al. Diet and reproductive hormones: a study of vegetarian and nonvegetarian postmenopausal women. J Natl Cancer Inst 1981:67:761–7.
19. Gandini S, Merzenich H, Robertson C, Boyle P. Meta-analysis of studies on breast cancer risk and diet: the role of fruit and vegetable consumption and the intake of associated micronutrients. Eur J Cancer 2000;36:636–46.
20. Smith-Warner SA, Spiegelman D, Yaun SS, et al. Intake of fruits and vegetables and risk of breast cancer. A polled analysis of cohort studies. JAMA 2001;285:769–76.
21. Smith-Warner SA, Spiegelman D, Yaun SS, et al. Intake of fruits and vegetables and risk of breast cancer. A polled analysis of cohort studies. JAMA 2001;285:769–76.
22. Levy J, Bosin E, Feldman B, et al. Lycopene is a more potent inhibitor of human cancer cell proliferation than either α-carotene or β-carotene. Nutr Cancer 1995;24:257–66.
23. Giovannucci E. Tomatoes, tomato-based products, lycopene, and cancer: review of the epidemiologic literature. J Natl Cancer Inst 1999;91:317–31.
24. Zheng W, Gustafson DR, Sinha R, et al. Well-done meat intake and the risk of breast cancer. J Natl Cancer Inst 1998;90:1724–9.
25. De Stefani E, Ronco A, Mendilaharsu M, et al. Meat intake, heterocyclic amines, and risk of breast cancer : a case-control study in Uruguay. Cancer Epidemiol Biomarkers Prev 1997;6:573–81.
26. Ambrosone CB, Freudenheim JL, Sinha R, et al. Breast cancer risk, meat consumption and N-acetyltransferase (NAT2) genetic polymorphisms. Int J Cancer 1998;75:825–30.
27. Bjeldanes LF, Morris MM, Felton JS, et al. Effect of meat composition and cooking conditions on mutagen formation in fried ground beef. J Agriculture Food Chem 1983;31:18–21.
28. Zheng W, Gustafson DR, Sinha R, et al. Well-done meat intake and the risk of breast cancer. J Natl Cancer Inst 1998;90:1724–9.
29. Zheng W, Deitz AC, Campbell DR, et al. N-acetyltransferase 1 genetic polymorphism, cigarette smoking, well-done meat intake, and breast cancer risk. Cancer Epidemiol Biomarkers Prev 1999;8:233–9.
30. Kaizer L, Boyd NF, Kriukov V, Tritchler D. Fish consumption and breast cancer risk: an ecological study. Nutr Cancer 1989;12:61–8.
31. Rose DP, Connolley JM. Omega-3 fatty acids as cancer chemopreventive agents. Pharmacol Ther 1999;83:217–44.
32. Dixon JM, McDonald C, Elton RA, et al. Risk of breast cancer in women with palpable breast cysts : a prospective study. Lancet 1999;353:1742–5.
33. Tavani A, Pregnolato A, La Vecchia C, et al. Coffee consumption and the risk of breast cancer. Eur J Cancer Prev 1998;7:77–82.
34. Lubin F, Ron E, Wax Y, Modan B. Coffee and methylxanthines and breast cancer: a case-control study. J Natl Cancer Inst 1985;74:569–73.
35. Rosenberg L, Miller DR, Helmrich SP, et al. Breast cancer and the consumption of coffee. Am J Epidemiol 1985;122:391–9.
36. Trichopoulou A, Katsouyanni K, Stuver S, et al. Consumption of olive and specific food groups in relation to breast cancer risk in Greece. J Natl Cancer Inst 1995;87:110–6.
37. La Vecchia C, Negri E, Franceschi S, et al. Olive oil, other dietary fats, and the risk of breast cancer (Italy). Cancer Causes Control 1995;6:545–50.
38. Martin-Moreno JM, Willett WC, Gorgojo L, et al. Dietary fat, olive oil intake and breast cancer risk. Int J Cancer 1994;58:774–80.
39. Shun-Zhang Y, Rui-Fang L, Da-Dao X, Howe GR. A case-control study of dietary and nondietary risk factors for breast cancer in Shanghai. Cancer Res 1990;50:5017–21.
40. Simonsen NR, Navajas JF-C, Martin-Moreno JM, et al. Tissue stores of individual monounsaturated fatty acids and breast cancer: the EURAMIC study. Am J Clin Nutr 1998;68:134–41.
41. Trichopoulou A, Katsouyanni K, Stuver S, et al. Consumption of olive and specific food groups in relation to breast cancer risk in Greece. J Natl Cancer Inst 1995;87:110–6.
42. La Vecchia C, Negri E, Franceschi S, et al. Olive oil, other dietary fats, and the risk of breast cancer (Italy). Cancer Causes Control 1995;6:545–50.
43. Martin-Moreno JM, Willett WC, Gorgojo L, et al. Dietary fat, olive oil intake and breast cancer risk. Int J Cancer 1994;58:774–80.
44. Kaizer L, Boyd NF, Kriukov V, Tritchler D. Fish consumption and breast cancer risk: an ecological study. Nutr Cancer 1989;12:61–8.
45. Fay MP, Freedman LS, Clifford CK, Midthune DN. Effect of different types and amounts of fat on the development of mammary tumors in rodents: a review. Cancer Res 1997;57:3979–88.
46. Armstrong B, Doll R. Environmental factors and cancer incidence and mortality in different countries, with special reference to dietary practices. Int J Cancer 1975;15:617–31.
47. Boyar AP, Rose DP, Loughridge JR, et al. Response to a diet low in total fat in women with postmenopausal breast cancer: a pilot study. Nutr Cancer 1988;11:93–9.
48. Bagga D, Ashley JM, Geffrey SP, et al. Effects of a very low fat, high fiber diet on serum hormones and menstrual function. Cancer 1995;76:2491–6.
49. Chlebowski RT, Blackburn GL, Buzzard IM, et al. Adherence to a dietary fat intake reduction program in postmenopausal women receiving therapy for early breast cancer. J Clin Oncol 1993;11:2072–80.
50. Boyd NF, Greenberg C, Lockwood G, et al. Effects at two years of a low-fat, high-carbohydrate diet on radiologic features of the breast: results from a randomized trial. J Natl Cancer Inst1997;89:488–96.
51. Jain M, Miller AB, To T. Premorbid diet and the prognosis of women with breast cancer. J Natl Cancer Inst 1994;86:1390–7.
52. Herbert JR, Hurley TG, Ma Yunsheng. The effect of dietary exposures on recurrence and mortality in early stage breast cancer. Breast Cancer Res Treat 1998;51:17–28.
53. Howe GR, Hirohata T, Hislop G, et al. Dietary factors and risk of breast cancer : combined analysis of 12 case-control studies. J Natl Cancer Inst 19990;82:561–9.
54. Toniolo P, Riboli E, Protta F, et al. Calorie-providing nutrients and risk of breast cancer. J Natl Cancer Inst 1989;81:278–6.
55. Holmes MD, Hunter DH, Colditz GA, et al. Association of dietary intake of fat and fatty acids with risk of breast cancer. JAMA 1999;281:914–20.
56. Jones DY, Schatzkin A, Green SB, et al. Dietary fat and breast cancer in the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study. J Natl Cancer Inst 1987;79:465–71.
57. Newman SC, Miller AB, Howe GR. A study of the effect of weight and dietary fat on breast cancer survival time. Am J Epidemiol 1986;123:767–74.
58. Howe GR, Friedenreich CM, Jain M, Miller AB. A cohort study of fat intake and risk of breast cancer. J Natl Cancer Inst 1991;83:336–40.
59. Trichopoulou A, Katsouyanni K, Stuver S, et al. Consumption of olive and specific food groups in relation to breast cancer risk in Greece. J Natl Cancer Inst 1995;87:110–6.
60. La Vecchia C, Negri E, Franceschi S, et al. Olive oil, other dietary fats, and the risk of breast cancer (Italy). Cancer Causes Control 1995;6:545–50.
61. Martin-Moreno JM, Willett WC, Gorgojo L, et al. Dietary fat, olive oil intake and breast cancer risk. Int J Cancer 1994;58:774–80.
62. Kaizer L, Boyd NF, Kriukov V, Tritchler D. Fish consumption and breast cancer risk: an ecological study. Nutr Cancer 1989;12:61–8.
63. Jones DY, Schatzkin A, Green SB, et al. Dietary fat and breast cancer in the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study. J Natl Cancer Inst 1987;79:465–71.
64. Newman SC, Miller AB, Howe GR. A study of the effect of weight and dietary fat on breast cancer survival time. Am J Epidemiol 1986;123:767–74.
65. Saskai S, Moracsek M, Kesteloot H. An ecological study of the relationship between dietary fat intake and breast cancer mortality. Prev Med 1993;22:187–202.
66. Armstrong B, Doll R. Environmental factors and cancer incidence and mortality in different countries, with special reference to dietary practices. Int J Cancer 1975;15:617–31.
67. Wu AH, Ziegler RG, Nomura AMY, et al. Soy intake and risk of breast cancer in Asians and Asian Americans. Am J Clin Nutr 1998;68(suppl):1437–43S [review].
68. Wu AH, Ziegler RG, Horn-Ross PL, et al. Tofu and risk of breast cancer in Asian-Americans. Cancer Epidemiol Biomarkers Prev 1996;5:901–6.
69. Messina MJ, Persky V, Setchell KDR, Barnes S. Soy intake and cancer risk: a review of the in vitro and in vivo data. Nutr Cancer 1994;21:113–31 [review].
70. Messina MJ. Legumes and soybeans: overview of their nutritional profiles and health effects. Am J Clin Nutr 1999;70(suppl):439–50S [review].
71. Barnes S. The chemopreventive properties of soy isoflavonoids in animal models of breast cancer. Breast Cancer Res Treat 1997;46:169–79 [review].
72. Hilakivi-Clarke L, Cho E, Onojafe I, et al. Maternal exposure to genistein during pregnancy increases carcinogen-induced mammary tumorigenesis in female rat offspring. Oncol Rep 1999;6:1089–95.
73. Hargreaves DNF, Potten CS, Harding C, et al. Two-week dietary soy supplementation has an estrogenic effect on normal premenopausal breast. J Clin Endocrinol Metab 1999;84:4017–24.
74. Petrakis NL, Barnes S, King EB, et al. Stimulatory influence of soy protein isolate on breast secretion in pre- and postmenopausal women. Cancer Epidemiol Biomarkers Prev 1996;5:785–94.
75. McMichael-Phillips DF, Harding C, Morton M, et al. Effects of soy-protein supplementation on epithelial proliferation in the histologically normal human breast. Am J Clin Nutr 1998;68(suppl):1431–6S.
76. Barnes S. The chemopreventive properties of soy isoflavonoids in animal models of breast cancer. Breast Cancer Res Treat 1997;46:169–79 [review].
77. Hilakivi-Clarke L, Cho E, Onojafe I, et al. Maternal exposure to genistein during pregnancy increases carcinogen-induced mammary tumorigenesis in female rat offspring. Oncol Rep 1999;6:1089–95.
78. Lu LJ, Anderson KE, Grady JJ, Nagamani M. Effects of soya consumption for one month on steroid hormones in premenopausal women: implications for breast cancer risk reduction. Cancer Epidemiol Biomarkers Prev 1996;5:63–70.
79. Nagato C, Takatsuka N, Inaba S, et al. Effect of soymilk consumption on serum estrogen concentrations in premenopausal Japanese women. J Natl Cancer Inst 1998;90:1830–5.
80. Hargreaves DNF, Potten CS, Harding C, et al. Two-week dietary soy supplementation has an estrogenic effect on normal premenopausal breast. J Clin Endocrinol Metab 1999;84:4017–24.
81. Petrakis NL, Barnes S, King EB, et al. Stimulatory influence of soy protein isolate on breast secretion in pre- and postmenopausal women. Cancer Epidemiol Biomarkers Prev 1996;5:785–94.
82. McMichael-Phillips DF, Harding C, Morton M, et al. Effects of soy-protein supplementation on epithelial proliferation in the histologically normal human breast. Am J Clin Nutr 1998;68(suppl):1431–6S.
83. Barnes S. The chemopreventive properties of soy isoflavonoids in animal models of breast cancer. Breast Cancer Res Treat 1997;46:169–79 [review].
84. Hilakivi-Clarke L, Cho E, Onojafe I, et al. Maternal exposure to genistein during pregnancy increases carcinogen-induced mammary tumorigenesis in female rat offspring. Oncol Rep 1999;6:1089–95.
85. Hargreaves DNF, Potten CS, Harding C, et al. Two-week dietary soy supplementation has an estrogenic effect on normal premenopausal breast. J Clin Endocrinol Metab 1999;84:4017–24.
86. Petrakis NL, Barnes S, King EB, et al. Stimulatory influence of soy protein isolate on breast secretion in pre- and postmenopausal women. Cancer Epidemiol Biomarkers Prev 1996;5:785–94.
87. McMichael-Phillips DF, Harding C, Morton M, et al. Effects of soy-protein supplementation on epithelial proliferation in the histologically normal human breast. Am J Clin Nutr 1998;68(suppl):1431–6S.
88. Messina MJ. Legumes and soybeans: overview of their nutritional profiles and health effects. Am J Clin Nutr 1999;70(suppl):439–50S [review].
89. Barnes S. The chemopreventive properties of soy isoflavonoids in animal models of breast cancer. Breast Cancer Res Treat 1997;46:169–79 [review].
90. Hilakivi-Clarke L, Cho E, Onojafe I, et al. Maternal exposure to genistein during pregnancy increases carcinogen-induced mammary tumorigenesis in female rat offspring. Oncol Rep 1999;6:1089–95.
91. Hargreaves DNF, Potten CS, Harding C, et al. Two-week dietary soy supplementation has an estrogenic effect on normal premenopausal breast. J Clin Endocrinol Metab 1999;84:4017–24.
92. Petrakis NL, Barnes S, King EB, et al. Stimulatory influence of soy protein isolate on breast secretion in pre- and postmenopausal women. Cancer Epidemiol Biomarkers Prev 1996;5:785–94.
93. McMichael-Phillips DF, Harding C, Morton M, et al. Effects of soy-protein supplementation on epithelial proliferation in the histologically normal human breast. Am J Clin Nutr 1998;68(suppl):1431–6S.
94. Messina M, Barnes S. The role of soy products in reducing risk of cancer. J Natl Cancer Inst 1991;83:541–6 [review].
95. Burley VJ. Sugar consumption and human cancer in sites other than the digestive tract. Eur J Cancer Prev 1998;7:253–77 [review].
96. Decarli A, Favero A, La Vecchia C, et al. Macronutrients, energy intake, and breast cancer risk: implications from different models. Epidemiology 1997;8:425–8.
97. Marcus PM, Newman B, Moorman PG, et al. Physical activity at age 12 and adult breast cancer risk (United States). Cancer Causes Control 1999;10:293–302.
98. Bullen BA, Skrinar GS, Beitins IZ, et al. Induction of menstrual disorders by strenuous exercise in untrained women. N Engl J Med 1985;312:1349–53.
99. Rockhill B, Willett WC, Hunter DJ, et al. A prospective study of recreational physical activity and breast cancer risk. Arch Intern Med 1999;159:2290–6.
100. Thune I, Brenn T, Lund E, Gaard M. Physical activity and the risk of breast cancer. N Engl J Med 1997;336:1269–75.
101. Gammon MD, Schoenberg JB, Britton JA, et al. Recreational physical activity and breast cancer risk among women under age 45 years. Am J Epidemiol 1998;147:273–80.
102. Gram IT, Funkhouser E, Tabar L. Moderate physical activity in relation to mammographic patterns. Cancer Epidemiol Biomarkers Prev 1999;8:117–22.
103. Segar ML, Katch VL, Roth RS, et al. The effect of aerobic exercise on self-esteem and depressive and anxiety symptoms among breast cancer survivors. Oncol Nurs Forum 1998;25:107–13.
104. Johnson KC, Hu J, Mao Y, & The Canadian Cancer Registries Epidemiology Research Group. Passive and active smoking and breast cancer risk in Canada, 1994–7. Cancer Causes Control 2000;11:211–21.
105. London SJ, Colditz GA, Stampfer JM, et al. Prospective study of smoking and the risk of breast cancer. J Natl Cancer Inst 1989;81:1625–31.
106. Gammon MD, Schoenberg JB, Teitelbaum SL, et al. Cigarette smoking and breast cancer risk among young women (United States). Cancer Causes Control 1998;9:583–90.
107. Lash TJ, Aschengrau A. Active and passive cigarette smoking and the occurrence of breast cancer. Am J Epidemiol 1999;149:5–12.
108. Gallo JJ, Armenian HK, Ford DE. Major depression and cancer: the 13-year follow-up of the Baltimore Epidemiologic Catchment Area sample (United States). Cancer Causes Control 2000;11:751–8.
109. Chen CC, David AS, Nunnerley H, et al. Adverse life events and breast cancer: case-control study. BMJ 1995;311:1527–30.
110. Geyer S. Life events prior to manifestation of breast cancer: a limited prospective study covering eight years before diagnosis. J Psychosomatic Res 1991;35:355–63.
111. Protheroe D, Turvey K, Horgan K, et al. Stressful life events and difficulties and onset of breast cancer: case-control study. BMJ 1999;319:1027–30.
112. Ramirez AJ, Craig TK, Watson JP, et al. Stress and relapse of breast cancer. BMJ 1989;298:291–3.
113. Roberts FD, Newcomb PA, Trentham-Dietz A, Storer BE. Self-reported stress and risk of breast cancer. Cancer 1996;77:1089–93.
114. Barraclough J, Pinder P, Cruddas M, et al. Life events and breast cancer prognosis. BMJ 1992;304:1078–81.
115. Tross S, Herndon J II, Korzun A, et al. Psychological symptoms and disease-free and overall survival in women with stage II breast cancer. J Natl Cancer Inst 1996;88:661–7.
116. Andersen BL, Farrar WB, Golden-Kreutz D, et al. Stress and immune response after surgical treatment for regional breast cancer. J Natl Cancer Inst 1998;90:30–6.
117. Levy SM, Herberman RB, Whiteside T, et al. Perceived social support and tumor estrogen/progesterone receptor status as predictors of natural killer cell activity in breast cancer patients. Psychosomatic Med 1990;52:73–85.
118. Andersen BL, Farrar WB, Golden-Kreutz D, et al. Stress and immune response after surgical treatment for regional breast cancer. J Natl Cancer Inst 1998;90:30–6.
119. Levy SM, Herberman RB, Whiteside T, et al. Perceived social support and tumor estrogen/progesterone receptor status as predictors of natural killer cell activity in breast cancer patients. Psychosomatic Med 1990;52:73–85.
120. Mausell E, Brisson J, Deschênes L. Social support and survival among women with breast cancer. Cancer 1995;76:631–7.
121. Pettingall KW, Morris T, Greer S, Haybittle JL. Mental attitudes to cancer: an additional prognostic factor. Lancet 1985;i:750.
122. Greer S, Morris T, Pettingale KW, Haybittle JL. Psychological response to breast cancer and 15-year outcome. Lancet 1990;335:49–50 [letter].
123. Watson M, Haviland JS, Greer S, et all. Influence of psychological response on survival in breast cancer: a population-based cohort study. Lancet 1999;354:1331–6.
124. Greer S, Moorey S, Baruch JDR, et al. Adjuvant psychological therapy for patients with cancer: a prospective randomised trial. Lancet 1992;304:675–80.
125. Simonton OC, Matthews-Simonton S. Cancer and stress. Counseling the cancer patients. Med J Aust 1981;1:679–83.
126. Grossarth-Maticek R, Eysenck HJ. Length of survival and lymphocyte percentage in women with mammary cancer as a function of psychotherapy. Psychol Rep 1989;65:315–21.
127. Spiegel D, Bloom JR, Kraemer HC, Gottheil. Effect of psychosocial treatment on survival of patients with metastatic breast cancer. Lancet 1989;ii:888–91.
128. Bridge LR, Benson P, Pietroni PC, Priest RG. Relaxation and imagery in the treatment of breast cancer. BMJ 1988;297:1169–72.
129. Spiegel D, Bloom JR. Group therapy and hypnosis reduce metastatic breast carcinoma pain. Psychosom Med 1983;45:333–9.
130. Gellert GA, Maxwell RM, Siegel BS. Survival of breast cancer patients receiving adjunctive psychosocial support therapy: a 10-year follow-up study. J Clin Oncol 1993;11:66–9.
131. Peacock SL, White E, Daling JR, et al. Relation between obesity and breast cancer in young women. Am J Epidmeiol 1999;149:339–46.
132. Rohan TE, Jain MG, Howe GR, Miller AB. Dietary folate consumption and breast cancer risk. J Natl Cancer Inst 2000;92:266–9.
133. Zhang S, Hunter DJ, Hankinson SE, et al. A prospective study of folate intake and the risk of breast cancer. JAMA 1999;281:1632–7.
134. Zhang S, Hunter DJ, Hankinson SE, et al. A prospective study of folate intake and the risk of breast cancer. JAMA 1999;281:1632–7.
135. Fex G, Pettersson B, Akesson B. Low plasma selenium as a risk factor for cancer death in middle-aged men. Nutr Cancer 1987;10:221–9.
136. Knekt P, Aromaa A, Maatela J, et al. Serum selenium and subsequent risk of cancer among Finnish men and women. J Natl Cancer Inst 1990;82:864–8.
137. Kok FJ, deBruijn AM, Hofman A, et al. Is serum selenium a risk factor for cancer in men only? Am J Epidemiol 1987;125:12–6.
138. Brock KE, Gridley G, Morris JS, Willett WC. Serum selenium level in relation to in situ cervical cancer in Australia. J Natl Cancer Inst 1991;83:292–3.
139. Knekt P, Aromaa A, Maatela J, et al. Serum selenium and subsequent risk of cancer among Finnish men and women. J Natl Cancer Inst 1990;82:864–8.
140. Kok FJ, deBruijn AM, Hofman A, et al. Is serum selenium a risk factor for cancer in men only? Am J Epidemiol 1987;125:12–6.
141. Hunter DJ, Morris JS, Stampfer MJ, et al. A prospective study of selenium status and breast cancer risk. JAMA 1990;264:1128–31.
142. Helzlsouer KJ, Alberg AJ, Norjus EP, et al. Prospective study of serum micronutrients and ovarian cancer. J Natl Cancer Inst 1996;88:32–7.
143. Vinceti M, Rovesti S, Gabrielli C, et al. Cancer mortality in a residential cohort exposed to environmental selenium through drinking water. J Clin Epidemiol 1995;48:1091–7.
144. Garland M, Morris JS, Stampfer MJ, et al. Prospective study of toenail selenium levels and cancer among women. J Natl Cancer Inst 1995;87:497–505.
145. Clark LC, Alberts DS. Selenium and cancer: risk or protection? J Natl Cancer Inst 1995;87:473–5 [editorial].
146. Clark LC, Combs GF Jr, Turnbull BW, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. JAMA 1996;276:1957–63.
147. Clark LC, Combs GF Jr, Turnbull BW, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. JAMA 1996;276:1957–63.
148. Thompson HJ, Meeker LD, Becci PJ, Kokoska S. Effect of short-term feeding of sodium selenite on 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis in the rat. Cancer Res 1982;42:4954–8.
149. Schrauzer GN, Ishmael D. Effects of selenium and of arsenic on the genesis of spontaneous mammary tumors in inbred C3H mice. Ann Clin Lab Sci 1974;4:441–7.
150. Schrauzer GN, Molenaar T, Mead S, et al. Selenium in the blood of Japanese and American women with and without breast cancer and fibrocystic disease. Jpn J Cancer Res (Gann) 1985;76:374–7.
151. McConnell KP, Jager RM, Bland KI, Blotcky AJ. The relationship of dietary selenium and breast cancer. J Surg Oncol 1980;15:67–70.
152. Hunter DJ, Morris JS, Stampfer MJ, et al. A prospective study of selenium status and breast cancer risk. JAMA 1990;264:1128–31.
153. Van’t Veer P, van der Wielen RPG, Kok FJ, et al. Selenium in diet, blood, and toenails in relation to breast cancer: a case-control study. Am J Epidemiol 1990;131:987–94.
154. Van den Brandt PA, Goldbohm A, van’t Veer P, et al. Toenail selenium levels and the risk of breast cancer. Am J Epidemiol 1994;140:20–6.
155. Van Noord PA, Collette HJ, Maas MJ, de Waard F. Selenium levels in nails of premenopausal breast cancer patients assessed prediagnostically in a cohort-nested case-referent study among women screened in the DOM project. Int J Epidemiol 1987;16:318–22.
156. Garland M, Willett WC, Manson JE, Hunter DJ. Antioxidant micronutrients and breast cancer. J Am Coll Nutr 1993;12400–11 [review].
157. Clark LC, Combs GF Jr, Turnbull BW, et al. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. JAMA 1996;276:1957–63.
158. Männistö S, Alfthan G, Virtanen M, et al. Toenail selenium and breast cancer––a case-control study in Finland. Eur J Clin Nutr 2000;54:98–103.
159. Torun M, Akgul S, Sargin H. Serum vitamin E level in patients with breast cancer. J Clin Pharmacol Ther 1995;20:173–8.
160. Wald NJ, Boreham J, Hawward JL, et al. Plasma retinol, ß-carotene and vitamin E levels in relation to the future risk of breast cancer. Br J Cancer 1984;49:321–4.
161. Kimmick GG, Bell RA, Bostick RM. Vitamin E and breast cancer: a review. Nutr Cancer 1997;27:109–17.
162. Gerber M, Richardson S, Crastes de Paulet P, et al. Relationship between vitamin E and polyunsaturated fatty acids in breast cancer. Cancer 1989;64:2374–53.
163. Gerber M, Cavallo F, Marubini E, et al. Liposoluble vitamins and lipid parameters in breast cancer. A joint study in northern Italy and southern France. Int J Cancer 1988;42:489–94.
164. Hunter DJ, Manson JE, Colditz GA, et al. A prospective study of the intake of vitamins C, E, and A and the risk of breast cancer. N Engl J Med 1993;329:234–40.
165. Knekt P. Serum vitamin E level and risks of female cancers. Int J Epidemiol 1988;17:281–8.
166. Pussinen PJ, Lindner H, Glatter O, et al. Lipoprotein-associated alpha-tocopheryl-succinate inhibits cell growth and induces apoptosis in human MCF-7 and HBL-100 breast cancer cells. Biochim Biophys Acta 2000;1485:129–44.
167. Gorham ED, Garland FC, Garland CF. Sunlight and breast cancer incidence in the USSR. Int J Epidemiol 1990;19:820–4.
168. Anzano MA, Smith JM, Uskokovic, et al. 1α,25-dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalciferol (Ro24–5531), a new deltanoid (vitamin D analogue) for prevention of breast cancer in the rat. Cancer Res 1994;54:1653–6.
169. Demdirpence E, Balaguer P, Trousse F, et al. Antiestrogenic effects of all-trans-retinoic acid and 1,25-dihydroxyvitamin D3 in breast cancer cells occur at the estrogen response element level but through different molecular mechanisms. Cancer Res 1994;54:1458–64.
170. John EM, Schwartz GG, Dreon DM, Koo J. Vitamin D and breast cancer risk: the NHANES I Epidemiologic follow-up study, 1971–1975 to 1992. Cancer Epidemiol Biomarkers Prev 1999;8:399–406.
171. Vink-van Wijngaarden T, Pols HA, Buurman CJ, et al. Inhibition of breast cancer cell growth by combined treatment with vitamin D3 analogues and tamoxifen. Cancer Res 1994;54:5711–7.
172. James SY, Merceer E, Brady M, et al. ERB1089, a synthetic analogue of vitamin D, induces apoptosis in breast cancer cells in vivo and in vitro. Br J Pharmacol 1998;125:953–62.
173. Eisman JA, Barkla DH, Tutton PJM. Suppression of in vitro growth of human cancer solid tumor xenografts by 1,25-dihydroxyvitamin D3. Cancer Res 1987;47:21–5.
174. Ravid A, Rocker D, Machlenkin A, et al. 1,25-dihydroxyvitamin D3 enhances the susceptibility of breast cancer cells to doxorubicin-induced oxidative damage. Cancer Res 1999;59:862–7.
175. Bower M, Colston KW, Stein RC, et al. Topical calcipotriol treatment in advanced breast cancer. Lancet 1991;337:701–2.
176. Colston KW, Berger U, Coombes RC. Possible role for vitamin D in controlling breast cancer cell proliferation. Lancet 1989;I:188–91.
177. Eisman JA, Suva LJ, Martin TJ. Significance of 1,25-dihydroxyvitamin D3 receptor in primary breast cancer. Cancer Res 1986;46:5406–8.
178. Freake HC, Abeyasekera G, Iwasaki J, et al. Measurement of 1,25-dihydroxyvitamin D3 receptors in breast cancer and their relationship to biochemical and clinical indices. Cancer Res 1984;44:1677–81.
179. Cos S, Fernández R, Güézmes A, Sánchez-Barceló EJ. Influence of melatonin on invasive and metastatic properties of MCF-7 human breast cancer cells. Cancer Res 1998;58:4383–90.
180. Mediavilla MD, Cos S, Sánchez-Barceló EJ. Melatonin increases p53 and p21 WAF1 expression in MCF-7 human breast cancer cells in vitro. Life Sci 1999;65:415–20.
181. Baldwin WS, Travlos GS, Risinger JI, Barrett JC. Melatonin does not inhibit estradiol-stimulated proliferation in MCF-7 and BG-1 cells. Carcinogenesis 1998;19:1895–1900.
182. Lissoni P, Barmo S. Meregalli S, et al. Modulation of cancer endocrine therapy by melatonin: a phase II study of tamoxifen plus melatonin in metastatic breast cancer patients progressing under tamoxifen alone. Br J Cancer 1995;71:854–6.
183. Neri B, De Leonardis V, Gemelli MT, et al. Melatonin as biological response modifier in cancer patients. Anticancer Res 1998;18:1329–32.
184. Lissoni P, Barni S, Crispino S, et al. Endocrine and immune effects of melatonin therapy in metastatic cancer patients. Eur J Cancer Clin Oncol 1989;25:789–95.
185. Lissoni P, Barni S, Ardizzoia A, et al. A randomized study with the pineal hormone melatonin versus supportive care alone in patients with brain metastases due to solid neoplasms. Cancer 1994;73:699–701.
186. Lissoni P, Barni S, Ardizzoia A, et al. Randomized study with the pineal hormone melatonin versus supportive care alone in advanced nonsmall cell lung cancer resistant to a first-line chemotherapy containing cisplatin. Oncology 1992;49:336–9.
187. Lissoni P, Paolorossi F, Tancini G, et al. Is there a role for melatonin in the treatment of neoplastic cachexia? Eur J Cancer 1996;32A:1340–3.
188. Lissoni P, Barni S, Tancini G, et al. A randomised study with subcutaneous low-dose interleukin 2 alone vs interleukin 2 plus the pineal neurohormone melatonin in advanced solid neoplasms other than renal cancer and melanoma. Br J Cancer 1994;69:196–9.
189. Lissoni P, Brivio F, Ardizzoia A, et al. Subcutaneous therapy with low-dose interlekin-2 plus the neurohormone melatonin in metastatic gastric cancer patients with low performance status. Tumori 1993;79:401–4.
190. Aldeghi R, Lissoni P, Barni S, et al. Low-dose interlekin-2 subcutaneous immunotherapy in association with the pineal hormone melatonin as a first-line therapy in locally advanced or metastatic hepatocellular carcinoma. Eur J Cancer 1994;30A:167–70.
191. Lissoni P, Paolorossi F, Tancini G, et al. A phase II study of tamoxifen plus melatonin in metastatic solid tumour patients. Br J Cancer 1996;74:1466–8.
192. Lissoni P, Barni S, Mandalà, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status. Eur J Cancer 1999;35:1688–92.
193. Lissoni P, Brivio O, Brivio F, et al. Adjuvant therapy with the pineal hormone melatonin in patients with lymph node relapse due to malignant melanoma. J Pineal Res 1996;21:239–42.
194. Neri B, Fiorelli C, Moroni F, et al. Modulation of human lymphoblastoid interferon activity by melatonin in metastatic renal cell carcinoma. Cancer 1994;73:315–9.
195. Jolliet P, Simon N, Barr J, et al. Plasma coenzyme Q10 concentrations in breast cancer: prognosis and therapeutic consequences. Int J Clin Pharmacol Ther 1998;36:506–9.
196. Lockwood K, Moesgaard S, Hanioka T, Folkers K. Apparent partial remission of breast cancer in “high risk” patients supplemented with nutritional antioxidants, essential fatty acids and CoQ10. Eighth International Symposium on the Biomedical and Clinical Aspects of Coenzyme Q10, Stockholm, Sweden, November, 1993.
197. Lockwood K, Moesgaard S, Hanioka T, Folkers K. Apparent partial remission of breast cancer in ‘high risk’ patients supplemented with nutritional antioxidants, essential fatty acids and coenzyme Q10. Molec Aspects Med 1994;5(Suppl):S231–40.
198. Lockwood K., Moesgaard S., Folkers K. Partial and complete regression of breast cancer in patients in relation to dosage of coenzyme Q10. Biochem Biophys Res Comm 1994;199:1504–8.
199. Lockwood K., Moesgaard S., Yamamoto T., Folkers K. Progress on therapy of breast cancer with vitamin Q10 and the regression of metastases. Biochem Biophys Res Comm 1995;212:172–7.
200. Lockwood K, Moesgaard S, Hanioka T, Folkers K. Apparent partial remission of breast cancer in ‘high risk’ patients supplemented with nutritional antioxidants, essential fatty acids and coenzyme Q10. Molec Aspects Med 1994;5(Suppl):S231–40.
201. Lockwood K, Moesgaard S, Hanioka T, Folkers K. Apparent partial remission of breast cancer in “high risk” patients supplemented with nutritional antioxidants, essential fatty acids and CoQ10. Eighth International Symposium on the Biomedical and Clinical Aspects of Coenzyme Q10, Stockholm, Sweden, November, 1993.
202. Lockwood K, Moesgaard S, Hanioka T, Folkers K. Apparent partial remission of breast cancer in ‘high risk’ patients supplemented with nutritional antioxidants, essential fatty acids and coenzyme Q10. Molec Aspects Med 1994;5(Suppl):S231–40.
203. Lockwood K., Moesgaard S., Folkers K. Partial and complete regression of breast cancer in patients in relation to dosage of coenzyme Q10. Biochem Biophys Res Comm 1994;199:1504–8.
204. Lockwood K., Moesgaard S., Yamamoto T., Folkers K. Progress on therapy of breast cancer with vitamin Q10 and the regression of metastases. Biochem Biophys Res Comm 1995;212:172–7.
205. Michnovicz JJ, Bradlow HL. Altered estrogen metabolism and excretion in humans following consumption of indole-3-carbinol. Nutr Cancer 1991;16:59–66.
206. Wattenberg LW, Loub WD. Inhibition of polycyclic aromatic hydrocarbon-induced neoplasia by naturally occurring indoles. Cancer Res 1978;38:1410–3.
207. Cover CM, Hsieh SJ, Cram EJ, et al. Indole-3-carbinal and tamoxifen cooperate to arrest the cell cycle of MCF-7 breast cancer cells. Cancer Res 1999;59:1244–51.
208. Riby JE, Chang GH, Firestone GL, Bjeldanes LF. Ligand-independent activation of estrogen receptor function by 3, 3’-diindolylmethane in human breast cancer cells. Biochem Pharmacol 2000;60:167–77.
209. McDougal A, Sethi Gupta M, Ramamoorthy K, et al. Inhibition of carcinogen-induced rat mammary tumor growth and other estrogen-dependent responses by symmetrical dihalo-substituted analogs of diindolylmethane. Cancer Lett 2000;151:169–79.
210. Walaszek Z, Szemraj J, Hanausek M, et al. D-glucaric acid content of various fruits and vegetables and cholesterol-lowering effects of dietary D-glucarate in the rat. Nutr Res 1996;16:673–81.
211. Heerdt AS, Young CW, Borgen PI. Calcium glucarate as a chemopreventive agent in breast cancer. Isr J Med Sci 1995;31:101–5.
212. Abou-Issa HM, Duruibe VA, Minton JP, et al. Putative metabolites derived from dietary combinations of calcium glucarate and N-(4-hydroxyphenyl)retinamide act synergistically to inhibit the induction of rat mammary tumors by 7,12-dimethylbenz[a]anthracene. Proc Natl Acad Sci 1988;85:4181–4.
213. Shamsuddin AM. Metabolism and cellular functions of IP6:a a review. Anticancer Res 1999;19:3733–6.
214. Cesano A, Visonneau S, Scimeca JA, et al. Opposite effects of linoleic acid and conjugated linoleic acid on human prostatic cancer in SCID mice. Anticancer Res 1998;18:1429-34.
215. Thompson H, Zhu Z, Banni S, et al. Morphological and biochemical status of the mammary gland as influenced by conjugated linoleic acid: implication for a reduction in mammary cancer risk. Cancer Res 1997;57:5067-72.
216. Ip C. Review of the effects of trans fatty acids, oleic acid, n-3 polyunsaturated fatty acids, and conjugated linoleic acid on mammary carcinogenesis in animals. Am J Clin Nutr 1997;66(suppl):1523S-29S [review].
217. Parodi PW. Cows’ milk fat components as potential anticarcinogenic agents. J Nutr 1997;127:1055-60 [review].
218. Dorant E, van der Brandt PA, Goldbohm RA. Allium vegetable consumption, garlic supplement intake and female breast carcinoma incidence. Br Cancer Res Treat 1995;33:163–70.
219. Challier B, Perarnau JM, Viel JF. Garlic, onion and cereal fibre as protective factors for breast cancer: A French case-control study. Eur J Epidemiol 1998;14:737–47.
220. Pedrinaci S, Algarra I, Garrido F. Protein-bound polysaccharide (PSK) induces cytotoxic activity in the NKL human natural killer cell line. Int J Clin Lab Res 1999;29:135–40.
221. Kidd PM. The use of mushroom glucans and proteoglycans in cancer treatment. Altern Med Rev 2000;5:4–27 [review].
222. Maehara Y, Moriguchi S, Sakaguchi Y, et al. Adjuvant chemotherapy enhances long-term survival of patients with advanced gastric cancer following curative resection. J Surg Oncol 1990;45:169–72.
223. Kidd PM. The use of mushroom glucans and proteoglycans in cancer treatment. Altern Med Rev 2000;5:4–27 [review].
224. Kaibara N, Soejima K, Nakamura T, et al. Postoperative long-term chemotherapy for advanced gastric cancer. Jpn J Surg 1976;6:54–9.
225. Niimoto M, Hattori T, Tamada R, et al. Postoperative adjuvant immunochemotherapy with mitomycin C, futraful and PSK for gastric cancer. An analysis of data on 579 patients followed for five years. Jpn J Surg 1988;18:681–6.
226. Nakazato H, Koike A, Saji S, et al. Efficacy of immunochemotherapy as adjuvant treatment after curative resection of gastric cancer. Lancet 1994;343:1122–6.
227. Ogoshi K, Satou H, Isono K, et al. Possible predictive markers of immunotherapy in esophageal cancer: retrospective analysis of a randomized study. Cancer Invest 1995;13:363–9.
228. Hayakawa K, Mitsuhashi N, Saito Y, et al. Effect of Krestin (PSK) as adjuvant treatment on the prognosis after radical radiotherapy in patients with non-small cell lung cancer. Anticancer Res 1993;13:1815–20.
229. Kondo M, Torisu M. Evaluation of an anticancer activity of a protein-bound polysaccharide PS-K (Krestin). In: Torisu M, Yoshida T (eds). Basic Mechanisms and Clinical Treatment of Tumor Metastasis. New York: Academic Press, 1985, 623–36.
230. Toi M, Hattori T, Akagi M, et al. Randomized adjuvant trial to evaluate the addition of tamoxifen and PSK to chemotherapy in patients with primary breast cancer. 5-year results from the Nishi-Nippon Group of the Adjuvant Chemoendorine Therapy for Breast Cancer Organization. Cancer 1992;70:2475–83.
231. Iino Y, Yokoe T, Maemura M, et al. Immunochemotherapies versus chemotherapy as adjuvant treatment after curative resection of operable breast cancer. Anticancer Res 1995;15:2907–12.
232. Morimoto T, Ogawa M, Orita K, et al. Postoperative adjuvant randomised trial comparing chemo-endocrine therapy, chemotherapy and immunotherapy for patients with stage II breast cancer: 5-year results from the Nishinihon Cooperative Study Group of Adjuvant Chemo-endocrine Therapy for Breast Cancer (ACETBC) of Japan. Eur J Cancer 1996;32A:235–42.
233. Gvamichava AR, Khatiashvili TM, Khudzhadze RG, et al. First results of the use of Eleutherococcus in the combined treatment of breast carcinoma. Lek Sredestva Dal’nego Vostoka 1966;7:231–5 [in Russian].
234. Kupin VI, Polevaia YeB, Sorokin AM. Stimulation of the immunological reactivity of cancer patients by Eleutherococcus extract. Vopr Onkol 1986;32:21–6 [in Russian].
235. Gvamichava AR, Khatiashvili TM, Khudzhadze RG, et al. First results of the use of Eleutherococcus in the combined treatment of breast carcinoma. Lek Sredestva Dal’nego Vostoka 1966;7:231–5 [in Russian].
236. Kupin VI, Polevaia YeB, Sorokin AM. Stimulation of the immunological reactivity of cancer patients by Eleutherococcus extract. Vopr Onkol 1986;32:21–6 [in Russian].
237. Kleijnen J, Knipschild P. Mistletoe treatment for cancer. Review of controlled trials in humans. Phytomedicine 1994;1:255–60 [review].
238. Dold U, Edler L, Mäurer HC, et al. Supplemental Cancer Therapy for Advanced Non-Small Cell Bronchial Carcinoma. Stuttgart: Georg Thieme Verlag, 1991.
239. Douwes FR, Kalden M, Frank G, Holzhauer P. Treatment of advanced colorectal carcinomas. Deutsch Z Onkol 1988;21:63–7 [in German].
240. Kjaer M. Mistletoe (Iscador) therapy in stage IV renal adenocarcinoma. Acta Oncol 1988;28:489–94.
241. Steuer-Vogt MK, Bonkowsky V, Ambrosch P, et al. The effect of an adjuvant mistletoe treatment programme in resected head and neck cancer patients: a randomised controlled clinical trial. Eur J Cancer 2001;37:23–31.
242. Heiny BM. Adjuvant treatment with standardized mistletoe extract reduces leukopenia and improves the quality of life of patients with advanced carcinoma of the breast receiving palliative chemotherapy (VEC regimen). Krebsmedizin 1991:12:3–14 [in German].
243. Nakachi K, Suemasu K, Suga K, et al. Influence of drinking green tea on breast cancer malignancy among Japanese patients. Jpn J Cancer Res 1998;89:254–61.
244. Nakachi K, Suemasu K, Suga K, et al. Influence of drinking green tea on breast cancer malignancy among Japanese patients. Jpn J Cancer Res 1998;89:254–61.
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