February 4th, marks World Cancer Day, a time to increase awareness and unity in the fight against this disease, responsible for 13% of all deaths worldwide in 2008. Breast cancer, in particular, kills more women than any other type, but research into diverse aspects of the disease continues to progress. Here, we take the opportunity to look at recent advances in understanding breast cancer risk and, from there, to controlling this disease.
The breast, more than most organs, goes through a multitude of changes throughout a woman’s life, from puberty, through pregnancy and breastfeeding, to menopause. All of these modifications leave the breast prone to cancer, because the more changes that take place, the more factors the breast is exposed to, and the more opportunity for something to go wrong. Indeed, breast cancer is the number one type of cancer in women, accounting for 16% of all female cases. And, of all cancer deaths in women, breast cancer is the leading cause. A great deal of research is currently taking place to dissect the mechanisms of this disease. Below are just a few of the recent projects addressing the question of breast cancer risk: how we can identify it and ways we can lower it, in the name of preventing the disease from ever taking hold.
Detecting Risk: Cellular Communication & Connexin 43
Just as in human relationships, communication is vital for cells. Interactions between them are important for their proper development and differentiation, or the taking on of a specific structure and function. This maturation depends on cells receiving the right signals, which is mediated by different types of junctions between them, explains Dana Bazzoun, who is researching the role of this process in breast cancer as part of her PhD work at the American University of Beirut.
“The hallmark of breast cancer is the disruption of communication between mammary epithelial cells. It’s vital to understand how this happens, step-by-step, leading to cancer initiation, progression and metastasis. First of all, we need to examine the interaction among the different cellular junctions—gap, tight and adherens junctions—to understand how the cancer is initiated.”"
Dana is interested in one specific protein making up the gap junction channel: connexin 43. “43” is believed to have an additional role in suppressing tumors, which it carries out by communicating with proteins inside the cell. These intermediaries are thought to relay the message from 43 all the way to the nucleus where it helps mediate the cell’s progression through its cycle of reproduction. It is here that many things can go awry and lead to cancer. Ms Bazzoun, therefore, wants to understand what happens downstream of connexin 43, in the molecular pathway that allows its signal to be transmitted.
In the lab of Dr. Rabih Talhouk, Dana and colleagues have looked at cancer cell lines from human breast tissue. Not only do these cells produce less connexin 43 than healthy ones, but it is also found inside the cell, in the cytosol, rather than in the cell membrane where this gap junction protein ought to be. When they pushed the cells to make more 43, it did position itself correctly in the membrane and many of the cancerous properties disappeared. The researchers may know why. Another protein, a transcription factor called b-Catenin, is known to shuttle between the nucleus and the cytoplasm, controlling the activity of a number of genes that encourage the proliferation and growth of cells. However, connexin 43 in the cell membrane binds to b-Catenin, leaving it less available to carry out its cancer-promoting activities. Inufficient connexin 43 in the membrane could mean a greater chance of cells becoming cancerous.
Dana Bazzoun’s project will look at this story the other way around, in order to establish a cause-and-effect relationship between connexin 43 expression and its location in the cell, and tumor initiation. As a recipient of the 2012 L’Oréal-UNESCO For Women in Science fellowships, she will explore this system with colleagues at Purdue University (Indiana, USA). Dana plans to take healthy human breast cells and try to block the production of connexin 43. Without this gap junction protein, will the normal cell become cancerous? If she can make this link, it could provide a biomarker for the detection of cancer—as well as reveal the relative influence of each type of junction in maintaining essential communication between cells.
Testing for low levels of 43 could allow doctors to detect an elevated risk of breast cancer before a tumor even forms. This would help patients to take precautions, such as going for frequent mammograms. For Ms Bazzoun,
“early detection of breast cancer is the most important aspect in decreasing the death rate from this disease. There are lots of risk factors we are bound by, but if we can develop strategies to detect potential risk of developing breast cancer we would still have the chance of protecting ourselves.”"
Risk Factors: The Role of Alcohol Nuanced
The factors correlated with an increased risk of breast cancer are numerous and, as Dana Bazzoun emphasizes, some can be difficult or impossible to avoid. We cannot change our family history of the disease; one’s socioeconomic status, linked to a higher risk, is difficult to control; and we may not even know what substances in our environment could be contributing to the development of cancer. Several recent studies, though, have at least helped to clarify the connection between alcohol and breast cancer. In one, scientists assessed the situation for girls with a family history of benign breast disease (BBD), known to be a risk factor for breast cancer. They found that women who consumed alcohol regularly as teenagers significantly increased their chances of developing BBD. The authors suggest that “adolescents with family history may reduce their risk by avoiding alcohol.”
While one study, published in November in the Journal of the American Medical Association, concluded that “Low levels of alcohol consumption were associated with a small increase in breast cancer risk”, another has just suggested that red wine might actually reduce one’s chances. In general, alcohol increases the body’s estrogen, which binds to cancer cells and encourages their proliferation. The new study, in the Journal of Women’s Health, suggests that elements found in grapes and red (but not white) wine may block estrogen production, lowering the odds of developing breast cancer. Further investigation, with a larger group of subjects, will be necessary to understand this effect better.
Regarding the many studies surrounding risk factors, Dana Bazzoun cautions that they often look at correlations or tendencies, while, in reality, many different factors are involved. The most important strategy against breast cancer, she feels, is for women who are genetically predisposed to take precautions, early and regularly, to increase their chances of beating this disease.