Doctors Redefine Breast Cancer Into 10 Subtypes in Study

Breast cancer stems from 10 genetic subtypes, not four as previously thought, according to a study published today in the journal Nature.

The findings by researchers in the U.K. and Canada will eventually enable doctors to better predict survival times in women with the disease and tailor the most appropriate treatment to their type of tumor, said Carlos Caldas, one of the authors and the chairman of cancer medicine at the University of Cambridge in England.

Tests to diagnose the new subtypes will probably be developed and in routine use in three to five years, which may not immediately affect how doctors work with patients, “but it’s surely going to change the way we do clinical trials,” Caldas said at a press conference in London yesterday. “It will lead to better treatments and more targeted treatments.”

Breast malignancies are diagnosed in 1.4 million women a year worldwide and are the most common cancers in women, according to Cancer Research UK. Survival rates after five years have increased to more than 80 percent from 50 percent in the late 1970s, according to the London-based charity.

The study by Cancer Research UK’s Cambridge Research Institute and the BC Cancer Agency in Vancouver looked at 2,000 frozen tumor samples from patients diagnosed with the disease at five hospitals. Scientists analyzed genetic material in the cancer cells for mutations and other changes and grouped them into 10 subtypes with common genetic features that correlated with long-term survival times.

‘Landmark’ Finding

The project was the largest global gene study of breast cancer, according to Cancer Research UK, which partly funded it. The charity’s chief executive, Harpal Kumar, said it represents a “landmark” in work on the disease.

The current practice of diagnosing and treating women with breast cancer involves testing tumor samples for the presence of genetic markers for two hormone receptors, known as ER and HER-2, Caldas said.

The outcome of that test determines which of four existing subtypes of breast cancer a woman has, and influences the treatment she receives and her prognosis, he said. The most common form is ER-positive and HER-2 negative breast cancer, which affects 70 percent of women with the disease, Caldas said. Another 15 percent have HER-2 positive tumors and can receive Roche Holding AG’s targeted medicine Herceptin, which costs 30,000 pounds ($48,000) a year and carries a risk of heart damage.

Personalized Medicines

Identifying the 10 subtypes means patients in the future will know more exactly which type of breast cancer they have and, as more targeted drugs are developed, they should receive more effective or personalized medicines, said Julia Wilson, head of research information at Breakthrough Breast Cancer.

“This is a massive step in the right direction for our understanding of what breast cancer is,” said Wilson, whose organization helped in the study by providing samples, data and analysis as well as one of the report’s authors. “It’s really helping us to make sure each patient gets the right treatment at the right time. And it’s really sparing them from grueling treatment if it’s not going to work.”

The new subtypes of breast cancer include seven that were defined as ER-positive and HER-2 negative, Caldas said. Survival times for each of the seven subtypes range from 80 percent after 15 years from diagnosis to less than 40 percent after 15 years, considered a wide variation, he said.

‘Quest’ for Detection

“We’ve been in a quest for finding better markers in that particular subgroup for the last 15 or 20 years,” he said. “This is much more discriminatory and informative.”

The study results should spur drugmakers to develop more drugs targeting tyrosine kinases, phosphatases and chromatin modifiers as possible treatments for the newly identified subtypes of breast cancer, Caldas said.

GlaxoSmithKline Plc’s Tykerb is a kinase inhibitor already approved for treating HER-2 positive breast cancer.

The findings may prompt drugmakers to take another look at existing compounds they had previously overlooked for the disease, said Karol Sikora, an oncologist at Hammersmith Hospital in London.

“It’s likely that a lot of drugs have been thrown out by pharmaceutical companies that would benefit small groups of patients,” Sikora said. “We call them ‘trash-can drugs’ in the business. Almost certainly in the junkyards of pharmaceutical companies are drugs that are active” against breast cancer.

Newly Discovered Genes

The study also identified several new genes that contribute to the disease, Caldas said. One of the subtypes has genetic markers that are associated with poor outcomes for patients, yet some patients with the subtype do well and defy predictions of their long-term survival. The immune system would appear to be “enriched” in women with this subtype and further understanding why might lead to new treatments, he said.

“It looks in this subset the immune system is playing a very active role in improving the prognoses of these women,” he said.

The breast-cancer study may also influence research on solid tumors affecting other organs, such as prostate, lung and colorectal cancers, Caldas said.

Cancer Research UK is funding a study that tests experimental treatments in 3,000 colorectal cancer patients with seven biomarkers, said Kate Law, director of clinical and population research at the charity. That study will begin in a few months, she said.

“Similar studies are begging to be done in other common human tumors,” Caldas said.

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