SAN ANTONIO (EGMN) – Truly large-scale prevention of breast cancer will require the development of a “hormonal vaccine” for young women that mimics the effects of repeated childbearing and breastfeeding, according to a prominent expert in cancer epidemiology.
“It’s not research that many people are doing. It’s not cutting edge. It won’t get into [the journals] Nature or Science. But it will get a Nobel Prize in Medicine,” Dr. Valerie Beral predicted at the San Antonio Breast Cancer Symposium.
More than 1 million new cases of breast cancer occur annually worldwide. It is known that relatively short-term exposure in early adulthood to the hormones of late pregnancy and lactation confers lifelong protection against the malignancy. No other preventive factor can approach the size of this protective effect. But it’s utterly unrealistic to expect women in developed countries to revert to such childbearing patterns.
That’s why a “hormonal vaccine” – something that can be given to young women for 9 months at a time, perhaps repeatedly, in order to mimic the effects of childbearing on breast tissue – is a must in order to achieve great success in breast cancer prevention. It’s badly needed not only in the developed world, but also in the major urban areas of the developing world, where the incidence of breast cancer is climbing rapidly, according to Dr. Beral, director of the cancer epidemiology unit and professor of epidemiology at the University of Oxford (England).
The notion that a major cause of breast cancer is small family size and a lack of prolonged breastfeeding is not new. It recapitulates an observation made by Dr. Bernardo Ramazzini, the Italian physician known as “the father of occupational medicine,” who in the early 1700s described breast cancer as “an occupational disease of nuns.”
“We’re all like nuns now,” Dr. Beral said. “Women in developing countries have had few or no children and haven’t breastfed. If there were large numbers of women in the West who’d had many children and kept breastfeeding for a long time, we’d see the difference, but we’re all like that now.”
Other modifiable risk factors for breast cancer draw a lot of attention, but the best estimates are that even if no women drank alcohol, were obese, or used hormone therapy, the U.S. incidence of breast cancer would drop only moderately, from 180,000 cases annually to 140,000.
“That’s a lot, but it’s still only about a 20% decrease,” she noted.
Dr. Beral cited World Health Organization data in support of her argument that drastically different childbearing and breastfeeding practices account for the great bulk of variation in breast cancer rates between the developed world, where the cumulative incidence to age 70 years is 6.3%, and rural areas of Asia and Africa, where the figure is just 1.0%.
Modeling studies indicate that if women in developed countries were to adopt the childbearing and breastfeeding practices that are the norm in rural Africa and Asia, their cumulative incidence of breast cancer to age 70 would plunge from 6.3% to 2.7%. Eliminating postmenopausal obesity, alcohol consumption, and hormone therapy would knock the rate down further to 1.6%, which is very close to the rate in the rural undeveloped world.
Genetic studies of breast cancer risk grab headlines. But when investigators at the University of Oxford–based Million Women Study (www.millionwomenstudy.org), for which Dr. Beral is the principal investigator, applied seven recently identified breast cancer risk alleles (N. Engl. J. Med. 2008;358:2796-803) to their massive study population, they found that in terms of risk conferred by the seven single nucleotide polymorphisms, the top quintile had a relative risk only about 1.5-fold greater than the lowest quintile.
“It’s not a huge variation in risk. It’s not as big as people perhaps might have wished to find,” she continued.
And that observation led Dr. Beral to what she stressed was the most important point of her plenary lecture: Few women in developed countries are at low risk of breast cancer.
“One in 10 women in developed countries will get breast cancer by age 80. The reason that 1 in 10 does and the other 9 don’t is largely chance. The people who get it are just unlucky, and the ones that don’t are lucky. There is, of course, some variation due to genes and other things, but the predominant factor is luck,” she said.
The Oxford-based Collaborative Group on Hormonal Factors in Breast Cancer, which meets every 5 years to analyze pooled data from roughly 100 epidemiologic studies worldwide, has shown that a woman’s breast cancer risk drops by about 10% for each live birth. Only term births count: Miscarriages and induced abortions have no impact on risk. It takes about 10 years for the preventive effect to appear, and then it persists for life.
What is it about term pregnancies and lengthy breastfeeding that confers delayed but subsequently lifelong protection against breast cancer? It’s not just the elevation in estrogen and progestins. The Collaborative Group and others have shown that oral contraceptives and hormone therapy are associated with increased breast cancer risk during their use and soon after, but a few years later the increased risk is gone.
“It’s not just estrogens and progestins that change during pregnancy. We have to be looking for something beyond,” Dr. Beral said.
She indicated she has no financial relationships relevant to her talk.
Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.
圣安东尼奥(EGMN)——如果我们想真正实现对乳腺癌的大范围预防，就必须为年轻女性研发一种“激素疫苗”，以模拟多次分娩和哺乳对机体产生的效应，据一位癌症流行病学领域的知名专家说。
“它即非当下的研究热点，也不是研究的最前沿。它甚至无法在《自然》或《科学》杂志上发表。但它的研制成功却能获得诺贝尔医学奖，”Valerie Beral博士在圣安东尼奥乳腺癌会议上预言道。
在世界各地，每年有超过100万例新发乳腺癌病例。已知在成年早期，对孕晚期及哺乳期机体所分泌激素的相对短期暴露可以对预防恶性肿瘤带来终身保护效应。而没有其他任何一种预防措施的保护性效应能与之媲美。但是很显然，期待发达国家的女性恢复这种生育方式是完全不现实的。
这就是为什么这种“激素疫苗”(为了模拟生育对乳腺组织的影响，每次年轻女性需要应用该疫苗9个月，有可能还需要重复使用)是达到成功预防乳腺癌的必要措施。目前，迫切需要该疫苗的不仅仅是发达国家，同时还包括发展中国家的主要城市地区在这些地区，乳腺癌的发病率正在迅速攀升，据英国牛津大学癌症流行病学研究中心主任和流行病学教授Beral博士说。
乳腺癌的主要发病原因是家庭小型化及哺乳时间过短，这已经不是一个全新的观点了。在18世纪初，被誉为“职业医学之父”的意大利医生Bernardo Ramazzini博士曾进行过一项观察性研究，他将乳腺癌描述为“修女的职业病”。
“我们现在都变得和修女一样了，”Beral博士说。“在发展中国家，许多女性极少甚至不生育，从而也就无法经历哺乳这一过程。在西方，如果现在有大量女性都生育很多孩子，并在很长时间内都保持母乳喂养，那么我们便能从中发现差别，但是现在我们似乎都极少生育了。”
乳腺癌的其他可控危险因素曾吸引了众多关注，但即便是基于这些因素均得以控制的最佳预测结果，即当所有女性都不再饮酒，不出现肥胖，也不使用激素替代疗法时，美国的乳腺癌发病率也仅会中等程度地下降，从每年180,000例下降到每年140,000例。
“那已经算得上显著变化了，但仍旧只下降了大约20%，”她指出。
Beral博士引用了世界卫生组织的数据来支持她的观点，即发达国家女性70岁前乳腺癌累计发病率是6.3%，而在亚洲和非洲的农村地区，该数据仅仅为1.0%，她认为，两地妇女截然不同的分娩和哺乳模式是造成这一差异的最主要原因。
建模研究表明，如果发达国家女性采用和亚洲和非洲农村地区女性一样的生育和哺乳模式，那么她们70岁前的乳腺癌累计发病率将会从6.3%骤降到2.7%。如果能消除绝经后肥胖，杜绝饮酒及使用激素替代疗法，那么这一数字会进一步下降至1.6%，这便和发展中国家农村地区的发病率极为接近了。
此外，乳腺癌风险的遗传学研究也是近期的头条新闻。但是当牛津大学的研究者们——基于一项由该校主持的百万女性研究项目(www.millionwomenstudy.org)，Beral博士是该项目的首席研究员——将近期确认的7个乳腺癌风险等位基因(N. Engl. J. Med. 2008;358:2796-803)用于这一大规模研究人群时，他们发现，如果以这7种单核苷酸多态性来衡量这一风险，则具有最高发病风险的1/5人群仅比最低风险的1/5人群的相对风险高出约1.5倍。
“这一风险差异并不明显。和人们期望中的数值相比，它显然太低了，”她补充道。
正是基于这一发现，Beral博士才强调说，这是她全体大会专题演讲中最重要的观点：在发达国家，几乎所有女性都处于乳腺癌的高发病风险中。
“在发达国家，每10名女性中就会有1名在80岁前发生乳腺癌。这10名女性中只有1人发病，而其他9人不发病，这一点在很大程度上是由运气导致的。那些发生乳腺癌的患者仅仅是因为运气欠佳，而那些未发病的人们则十分好运。当然还有另外一些原因导致这一差异，譬如基因的差异及其他原因，但最重要的原因还是运气，”她说道。
据牛津大学乳腺癌激素因素协作组表示，一位女性每成功产下一名胎儿，她的乳腺癌发病风险就下降大约10%，这一小组每5年召开一次会议，以对来自大约100项流行病学研究的汇总数据进行分析。只有足月分娩才被纳入计算：流产和人工流产对发病风险没有影响。大约需要10年的时间，保护性效应才会出现，然后便能持续终生。
对于预防乳腺癌，为何足月妊娠和足够长的哺乳时间可以提供迟发性且随后持续终生的保护性效应呢？这不仅仅和雌激素与孕激素的升高有关。协作组及其他研究结果表明，使用口服避孕药和激素替代疗法均和乳腺癌的发病风险增高有关，但这一风险仅仅存在于使用过程中，及之后不长的一段时间内，在数年后这一风险就消失了。
“在妊娠期间，并非只有雌激素和孕激素发生了改变。我们必须去寻找其他原因，”Beral博士说。
她声明没有任何相关的经济利益冲突。
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