Breast Cancer Is 10 Diseases Says Landmark Study
Then gradually, as mapping techniques improve, the data becomes more detailed and more precise.
The METABRIC team now has a detailed “map” of thousands of individual tumors that have been analyzed and re-analyzed in many different ways and linked to detailed information about the fate of the women they came from.
Not only has the team performed all kinds of analysis on the DNA of the tumors (for instance the map is now annotated with copy number changes and single letter variations or SNPs, for each tumor), it has also conducted a detailed analysis of their RNA so they can tell which genes were active in each sample. Altogether they did this for more than 30,000 types of RNA, each corresponding to the activity of a single gene.
- Mammography screening has led to a dramatic increase in the incidence of ductal carcinoma in situ (DCIS). The diagnosis was relatively rare before the early 1980’s and the widespread use of mammography. Today, approximately one woman is diagnosed with DCIS for every four women diagnosed with invasive breast cancer (Allegra et al, 2010).
- All women are at risk for breast cancer. Only 5-10% of those with breast cancer have inherited a mutation in the known breast cancer genes (BRCA1 and BRCA2) and 90-95% of breast cancer cases do not involve these inherited mutations. (ACS 2010; NCI 2006).
- Factors that increase a woman’s risk of breast cancer include older age, genetic factors, family history of breast or ovarian cancer, long menstrual history, null parity (having no children), older than 30 years of age at first full-term pregnancy, daily alcohol consumption, use of combined postmenopausal hormone replacement therapy (HRT), postmenopausal obesity and ionizing radiation. Factors that decrease a woman’s risk of breast cancer include breast-feeding and physical activity (exercise) (ACS, 2010).
- There is some new data to suggest that these risk factors have less influence among Hispanic women. According to results of the 4-Corners Breast Cancer Study, Hispanic women with breast cancer were more likely than white women with breast cancer to have characteristics associated with a lower risk of breast cancer, such as younger age at first birth, having more children, less hormone use, and less alcohol consumption (Hines et al, 2010).
- Higher breast density has been shown to be associated with the risk of breast cancer. It was found that the rate of breast cancer was almost four times greater in those with extremely dense breast tissue as opposed to those with fatty breast tissue. It is important to remember that since mammography is less sensitive in detecting breast cancer for dense breasts, the effect of breast density may be somewhat underestimated (Barlow et al, 2006).
- Studies on chemo preventive agents tamoxifen and raloxifene were not adequately designed to determine their impact on the prevention of breast cancer for healthy women, nor are the studies long enough to assess long term side effects and impact on mortality (Vogel et al, 2010).
“We’ve drilled down into the fundamental detail of the biological causes of breast cancer,” said Caldas, “we’ve moved from knowing what a breast tumour looks like under a microscope to pinpointing its molecular anatomy”.
“Our results will pave the way for doctors in the future to diagnose the type of breast cancer a woman has, the types of drugs that will work, and those that won’t, in a much more precise way than is currently possible,” he added.
Aparicio said:
“The new molecular map of breast cancer points us to new drug targets for treating breast cancer and also defines the groups of patients who would benefit most.”
Caldas said these results will not affect women diagnosed with breast cancer today, but he envisages future breast cancer patients will receive treatments tailored specifically to the genetic fingerprints of their tumors.
From this huge leap forward, the next step is to find out how the tumors in each of subgroup behave. How fast do they grow and spread?
Caldas said we also need to do more studies, both in the lab and in patients, to confirm the most effective treatments for each of the 10 types of breast cancer.
“The size of this study is unprecedented and provides insights into the disease such as the role of immune response, which will stimulate other avenues of research,” added Aparicio.
Kumar said the study marks the result of decades of research by Cancer Research UK to find the causes and drivers of breast cancer and enables a further step-change for patients with breast cancer.
“We’re entirely funded by the generosity of the public and this incredible support has put us at the heart of progress that’s underpinned the dramatic increase in the number of women surviving from breast cancer in the UK,” he added.
Caldas had this to say to the patients behind the study:
“I want to stress, this study wouldn’t have been possible without the breast cancer patients who donated their samples and agreed to take part in the study. None of this would have happened without them, and I’m so grateful for their participation.”
For an excellent account of how we have increased our understanding of breast cancer, plus a table showing the 10 disease subtypes, see Henry Scowcroft’s post in the Cancer Research UK Science Update blog.
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Written by Catharine Paddock PhD