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October 18, 2008

Caffeine and Nicotine May Influence Breast Cancer Risk

Author: Roxanne Nelson

October 17, 2008 — The consumption of caffeine is not linked to an overall increase in breast cancer, according to a report published in the October 13 issue of the Archives of Internal Medicine. However, the study does note that that a high consumption of caffeine might increase the risk for breast cancer in women with a history of benign breast disease.
The researchers also found a significant positive association between a high intake of caffeine and risk for breast tumors that were estrogen-receptor negative and progesterone-receptor negative (ER−PR−) or that were larger than 2 cm.
Separately, a new study published in the October 15 issue of Cancer Research suggests a possible role for nicotine in breast tumor development and metastases. Although the research is very preliminary, the study suggests that nicotine might be a component in the initiation of breast cancer induced by second-hand smoke.
"It is still unclear about the etiological role of cigarette smoke, including second-hand smoke, in the initiation and development of breast cancer," said lead author Chang Yan Chen, PhD, MD, from the department of radiology at Beth Israel Deaconess Medical Center, in Boston, Massachusetts. "Our study with nicotine only provides a possible aspect for further investigation."
Caffeine and Breast Cancer Risk
Although caffeine was thought to increase risk for breast cancer after research showed that eliminating dietary caffeine relieved symptoms in women with benign breast disease, a risk between caffeine consumption and breast cancer has not been established. Results of clinical trials have been inconsistent regarding the elimination or reduction of caffeine consumption and the development of benign breast disease.
In addition, most case–control studies have not found an association between caffeine from caffeinated beverages and foods and the risk for breast cancer, although several have reported either an inverse association or a weak positive association.
This study was conducted by Ken Ishitani, MD, PhD, from Brigham and Women's Hospital and Harvard Medical School, in Boston, and from Tokyo Women's Medical University, in Japan, and colleagues. They evaluated the association between caffeine consumption and breast cancer risk among participants of the Women's Health Study, analyzing dietary information from a cohort of 38,432 women, 45 years or older, between 1992 and 1995, who were free of cancer.
The women were followed for a period of approximately 10 years and, during the time, 1188 of the women developed invasive breast cancer.
There was no overall association between caffeine consumption and risk for breast cancer. However, among women with benign breast disease, the researchers found a borderline significant positive association with breast cancer risk among women in the highest quintile of caffeine consumption (relative risk [RR], 1.32), and for those who consumed 4 or more cups of coffee a day (RR, 1.35). A separate analysis showed a significant positive association between caffeine intake and risk for ER−PR− breast cancer (RR, 1.68). In addition, a significant positive association was shown for caffeine consumption and the risk of developing tumors larger than 2 cm (RR, 1.79).
"These findings indicate that caffeine consumption may affect breast cancer progression, and such an effect may be independent of the estrogen pathway," the researchers write. "These data suggest that high caffeine consumption may increase the risk of breast cancer in women with a history of benign breast disease or in breast tumors that are ER−PR− or larger than 2 cm, but these findings may be due to chance and warrant further study."
This study was supported by grants from NIH. The researchers have disclosed no relevant financial relationships.

Nicotine and Breast Cancer Development

In the second study, Dr. Chen and colleagues investigated the effect of nicotine on breast tumor development. They found that by interacting with receptors, nicotine can stimulate breast cancer tumorigenesis and progression by initiating a signaling cascade that involves protein kinase C (PKC) and cdc42. The investigation suggests that nicotine mobilizes PKC and cdc42 signaling in both normal breast cells and cancer cells to promote cell migratory activity.
This research is still is very experimental, Dr. Chen explained. "We do not intend to claim an association between nicotine and breast cancer. Our study only presents an observation or possible aspect for understanding the correlation between cigarette smoke — active or passive smoking — and the initiation or development of breast cancer."
Through a series of in vitro tests, the researchers found that human mammary epithelial-like MCF10A cells and cancerous MCF7 cells express at least 4 subunits of nicotine acetylcholine receptor. When bound, they can initiate a signaling process that potentially increases cell growth and migration.
"Our study, using cultured cell or implanted mouse system, showed that nicotine appears to promote the migration of breast epithelial-like or cancer cells," Dr. Chen told Medscape Oncology. "However, nicotine is not a conventional carcinogen, but rather it combines with other yet-to-be-determined factors to enable tumorigenesis, including breast cancer."
Nicotine was originally thought to be primarily responsible for tobacco addiction, but many studies now report that nicotine has the ability to modulate various key biological activities in nonneuronal tissues, the authors note. Of particular importance is that nicotine appears to promote the survival of numerous cell types, including keratinocytes and head or neck tumor cells.
"Nicotine receptor expresses in many types of nonneuronal cells," said Dr. Chen. "And our study showed that the engagement of nicotine receptor is able to activate growth-related processes. Therefore, people with different genetic predispositions may have different susceptibilities to nicotine-mediated progrowth signaling. "
Hence, she concluded, this "suggests a caution for the use of nicotine." As if there wasn't enough research already providing good reasons not to smoke.
The study was supported by the Flight Attendant Medical Research Institute and NIH grants. The researchers have disclosed no relevant financial relationships.
Arch Intern Med. 2008;168:2022-2031. AbstractCancer Res. 2008;68:8473-8480.

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