Skip to 0 minutes and 14 secondsBreast cancer has a much better outlook than many common cancers. In the UK, five-year survival is about 85%. Fewer than one person in five with stomach cancer will still be alive then, and fewer than one in 10 with lung cancer. Maximising the chance of long-term survival requires treatment carefully tailored to each patient and her particular cancer. Surgery and radiotherapy mainly target the breast itself and nearby tissues. Cytotoxic chemotherapy and hormonal treatments reach all parts of the body, so they are especially valuable if a breast cancer has spread in the blood stream to involve far away tissues, sometimes in several different parts of the body at the same time. This is called metastasis.
Skip to 1 minute and 5 secondsChemotherapy and hormonal treatments are also recommended for women at risk of their cancer coming back-- sometimes, years later. This can happen even if there is no sign the cancer has spread when it is first discovered and treated. This additional precautionary treatment is called adjuvant therapy. Three independent prognostic factors-- cancer size, stage, and grade-- are combined in the Nottingham prognostic index, or NPI, which helps the breast cancer team to know whether to advise adjuvant cytotoxic chemotherapy, or whether to offer adjuvant radiotherapy after a mastectomy to minimise the risk of local cancer recurrence. These 20 consecutive breast cancers show how much variation there is between cancer cells in different cases.
Skip to 2 minutes and 3 secondsThey have been arranged from low-grade, at the top, to high-grade, at the bottom of the picture. Of course, there are also many invisible differences between cases as well. This is also a risk marker for recurrence. These are cancer cells in a lymphatic vessel, in which they can travel to another part of the breast, local lymph nodes, and, eventually, the bloodstream. NPI prognostic groups were based on survival data for patients treated in the 1970s. Treatment outcomes are now much better, partly because the NPI helped us to understand who was at high risk of cancer progression and would benefit most from treatment to deal with that risk. These graphs tell a dramatic story.
Skip to 2 minutes and 54 secondsOn the left, is survival, stratified by NPI, for patients treated in the 1970s and 1980s. Fewer than one in five women in the poor prognostic group were still alive after 10 years. On the right, is survival data for women starting treatment 25 years later. The outlook for women in the worst prognostic group has been transformed, with over 75% still being alive at 10 years. This dramatic improvement was mainly achieved by better team working and consistent use of established treatments for the right people. These include hormonal treatments, such as the estrogen-blocking drug, tamoxifen, and aromatase inhibitors, which prevent oestrogen synthesis in post-menopausal women.
Skip to 3 minutes and 47 secondsBecause these drugs are only effective in the treatment of cancers which are making their own oestrogen receptors and progesterone receptors, ER and PR, all breast cancers must be tested to discover their ER and PR status. Oestrogen receptor testing, formerly used biochemical analysis of a piece of tumour tissue. False positive and false negative results could occur if there weren't enough cancer cells in the sample or there were too many normal breast epithelial cells, which also contain oestrogen and progesterone receptors. Diagnostic biopsies or therapeutic excisions will usually provide suitable tissue for ER and PR testing by immunohistochemistry on thin sections of formaldehyde-fixed, paraffin-embedded tissues, embedded in paraffin wax.
Skip to 4 minutes and 43 secondsThe pathologist undertaking microscopy can see exactly which cells contain the hormone receptors, confirming the presence of cancer cells and a satisfactory sample for testing. Test results are often given as the Allred score, which combines the percentage of cancer cells with hormone receptor staining and the intensity of staining. Maximum possible score is eight. Even a cancer with a lowish Allred score of three or four may respond to hormonal treatment. But if the score is zero for both ER and PR, as it was in this case, there is no real chance of any useful response to hormonal treatment. Staining of normal breast tissue adjacent to the cancer is a useful confirmation that the immunohistochemistry has worked properly.
Skip to 5 minutes and 43 secondsSo far, we have not talked about monoclonal antibody treatments. These target molecules important for specific cancers. Rituximab targets CD20 molecules on B cell lymphomas. And trastuzumab, or herceptin, targets HER2/neu, a tyrosine kinase signalling molecule related to epidermal growth factor receptor. Too many copies of the HER2 gene cause HER2 protein overproduction by about 15% of breast cancers. Metastatic, HER2-positive cancers may respond to herceptin, and it also works as an adjuvant treatment, but again, only if the cancer is HER2-positive. HER2 testing recognises scores of zero and one plus, which both count as negative, and three plus, which is definitely positive. Between these groups lie two plus cases, not obviously negative or positive.
Skip to 6 minutes and 48 secondsThese are investigated further by fluorescence in situ hybridisation, with probes for the HER2 gene on the long arm of chromosome 17 and for the centromere of chromosome 17 itself. A case may be judged non-amplified, borderline-amplified, or definitely amplified, based on the ratio of HER2 to chromosome 17. ER, PR, and HER2 status are especially significant, because they predict the likely response to important treatments and help, therefore, in choosing people likely to benefit from these treatments, while avoiding their use in women not likely to benefit, but who might still experience toxic side effects. Everyone involved in the care of women with breast cancer needs to know that diagnostic testing is complex and not immune to error.
Skip to 7 minutes and 43 secondsIn several laboratories, organisational problems have led to erroneous reports being issued. No laboratory can be complacent about this. Positive and negative controls, with internal and external quality monitoring, are essential to make sure laboratories deserve the trust of women with breast cancer who are relying on us to get it right for them.
The beginning of personalised treatment: breast cancer (8.11)
Dr James Going describes how targeted therapies have revolutionised outcomes in breast cancer prognosis.
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