Breast cancer treatments, mysteries advance in Philadelphia-area hospitals

Despite advances in thinking and treatment, scientists have not deciphered the mysteries of breast cancer.

Posted: October 03, 2011

In 1984, a retired Columbia University surgeon published a paper about his 47 years of experience with the "Halsted radical mastectomy," which involved removing a woman's cancerous breast, chest muscles, underarm lymph nodes, and sometimes part of her chest wall.

It was a disfiguring and debilitating operation and, as the surgeon, Cushman D. Haagensen, stated, for the many women found to have advanced disease, it was futile. Even so, he considered it the best available treatment and was dismayed that it was being abandoned in favor of more conservative surgery combined with radiation and chemotherapy.

"The threat of the physical penalty of radical mastectomy . . . weighs heavily with the patient," Haagensen lamented in Annals of Surgery. "Survival should be much more important to her."

Articles like his provide a stark measure of how far medical science has come in understanding, detecting, and treating breast cancer.

The 1980s saw the advent of screening mammography; breast-conserving lumpectomy; a hormonal drug that thwarts recurrence; and chemotherapies that kill the invisible threat - microscopic metastases.

Still, breast cancer is a formidable, flourishing foe. Despite the development of molecularly targeted therapies such as Herceptin, scientists have not deciphered the biology of the disease, especially its most aggressive forms. Even now, the only truly effective way to prevent it is to cut off healthy breasts, a radical resort that has become more common with the mid-1990s discovery of inherited breast cancer-predisposition genes, BRCA1 and BRCA2.

Equally disturbing, breast cancer incidence is rapidly increasing in developing countries as they embrace Western ways such as delayed childbearing, smaller families, and richer diets.

Peggy Porter, a Seattle cancer biology researcher, wrote about the issue in a 2008 editorial in New England Journal of Medicine. "Such countries," she stated, "now face the challenge of effectively detecting and treating a disease that previously was considered too uncommon to merit the allocation of precious health-care dollars."

Estrogen, the quintessential female hormone, plays a crucial - and poorly understood - role in breast cancer. In essence, the more lifetime estrogen exposure, the more chance of breast cancer. Menstruation at an early age, menopause at a late age, delayed childbearing or none, and not breast-feeding increase breast cancer risk. Estrogen exposure can also be boosted by body fat, which produces the hormone after the ovaries shut down at menopause, and by substances that behave like estrogen in the body, including some pollutants.

Most experts believe reduced estrogen exposure is why U.S. breast cancer incidence plunged an unprecedented 7 percent in 2003, the year after millions of women abruptly stopped taking menopausal hormone supplements. Their stampede followed a huge federal study that revealed the risks of long-term estrogen-progestin therapy outweighing the benefits.

That 2003 decline was the first in seven decades. Since 2004, U.S. rates have held fairly steady at about 125 cases per 100,000 women - one of the highest rates in the world.

Although American women now have a 12 percent (1 in 8) lifetime chance of getting the dreaded diagnosis, their chance of survival has never been better. Death rates have been falling about 2 percent a year since 1990.

Some experts argue that breast cancer is being overdiagnosed and overtreated, a result of mammography and early detection.

"We have detected a large amount of disease not destined to seriously harm or kill and - until quite recently - have not made significant progress in treating cancer," University of Pennsylvania physician Robert A. Aronowitz declares in his book Unnatural History: Breast Cancer and American Society. [Q&A with Dr. Aronowitz, Page 14.]

But distinguishing lethal cancers from nonlethal types is difficult - and dicey.

A subtype called "triple negative" breast cancer is known to be particularly aggressive and hard to treat because the tumor lacks the three molecular receptors that fuel most malignancies and that make chemotherapy effective. For unknown reasons, African American women are more likely than white women to develop this subtype.

At the other extreme, very early cancers still confined to the milk ducts - called ductal carcinoma in situ (DCIS) - may never invade surrounding tissue. Sixty thousand DCIS cases are diagnosed in the United States each year, accounting for about one out of every five new breast cancer cases.

But few women - or doctors - would opt to wait to see whether an early and readily eradicated cancer becomes one that could seriously harm or kill.

A recent development that is helping with treatment dilemmas involves molecular profiling tests, notably Oncotype DX, made by the biotech company Genomic Health.

Oncologist Lawrence Wickerham, associate chairman of a Pittsburgh-based research network, said the test had led to "a decrease in the use of chemotherapy," saving an estimated $100 million in health care costs, as well as wear and tear on patients.

Genomic Health is developing a test to help identify which pre-invasive cancers are unlikely to progress if treated minimally.

But such tests - which cost thousands of dollars, usually out of pocket - are not infallible and leave those women at medium risk with wrenching choices.

"The next step," Wickerham said, "will be using molecular information to identify which therapies women will benefit most from."

While the Western world moves toward the dream of "personalized" diagnosis and treatment, developing countries barely have the resources to track the growing scourge of the disease itself.

Indeed, the first rigorous global analysis of breast cancer - based on cancer registries, vital statistics data, and autopsy records - was published just last month in the Lancet.

The study, led by researchers at the University of Washington, found the number of cases diagnosed annually worldwide had risen dramatically from about 640,000 in 1980 to 1.6 million in 2010, with more than half of new cases occurring in developing countries.

While some of that increase reflected population growth, the researchers found that the lifetime chance of developing breast cancer in poor countries has steadily grown over the past 30 years. Consider a few examples: The risk has grown from less than 3 percent to more than 6 percent in Pakistan, from about 4 percent to 9.7 percent in Lebanon, and from less than 2 percent to 4.7 percent in Botswana.

The risk has also doubled or tripled in high-income Asian countries such as Japan, Singapore, and Taiwan where breast cancer was historically rare, bolstering the belief that Westernization fuels the trend.

Another disturbing finding was that an unexpectedly high proportion of patients who died in poor countries were women under 50, when breast cancer is relatively rare. In 2010, for example, 68,000 of the 425,000 women who died of the disease were 15 to 49. In many of these countries, breast cancer is now competing with childbirth as a major cause of death among adult women, said Rafael Lozano, a University of Washington global health researcher and coauthor of the study.

"I believe this shift is the most important," he said. "We are seeing more new cases and deaths in women at a reproductive age."

Hopefully, he said, the numbers will lead to changes in public health priorities, putting breast cancer on the agenda of world health agencies, philanthropies, and governments.

"Now that we have enough evidence to act," he said, "it should be hard to refuse to invest more resources."


Contact staff writer Marie McCullough at 215-854-2720 or mmccullough@phillynews.com.

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