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Skip to 0 minutes and 15 seconds Who was Sir George Thomas Beatson and why do we remember him? The short answer is that he was a Glasgow-based surgeon and we remember him for his contribution to the treatment of breast cancer. We can trace a path through his work to the anti-estrogen Tamoxifen which was probably the first targeted therapy and, so far, one of the most successful. Tamoxifen was the treatment of choice for a majority of breast cancer until recently, when better ways of attacking the estrogen-dependence of breast cancers were developed. Beatson was born in Sri Lanka in 1848, back when it was called Ceylon, while his father was on a tour of duty with the Indian army.

Skip to 0 minutes and 54 seconds He moved to Scotland as a boy and, following an undergraduate degree from Cambridge, gained a medical degree from Edinburgh University where he did part of his training with Lister, the pioneer of antiseptic surgery. He then settled in Glasgow and went on to become the director of the Glasgow Cancer Hospital. He is still commemorated in Glasgow by the Beatson West of Scotland Cancer Centre and the Beatson Institute of Cancer Research where some of the other presenters in this course are based. Beatson’s obituary describes him as a tall, commanding figure, a man of energy and determination. He was clearly a man who got things done. And his achievements included major contributions to establishing the St.

Skip to 1 minute and 33 seconds Andrew’s ambulance service and Scottish Red Cross across Scotland. He also set up a home nursing service that revolutionised patient care, which demonstrates his characteristic concern for the welfare of his patients. He was described as very tender with anyone in suffering. His focus on alleviating pain and suffering seems to have been a major motivation for Beatson’s work on breast cancer, which was published in this issue of The Lancet from 1896. Beatson had studied lactation and use in his MD thesis, and knew that removing the ovaries affected the proliferation of the mammary epithelial. He then developed the theory that removing the ovaries might also arrest the proliferation of breast cancer and lead to its degeneration.

Skip to 2 minutes and 19 seconds His famous Lancet paper describes three case studies where he tested this theory in patients with inoperable breast cancer, then an all too common occurrence. The first patient was referred to him with a tumor roughly the size of a tennis ball and ulcerating secondary growths. She was in pain, pale, and careworn and facing a dismal future. In Beatson’s words, “Once a case of cancer has passed beyond the reach of the surgeon’s knife, our curative measures are practically nil.” At the time, x-rays were just being discovered so radiotherapy was some years away. And chemotherapy was not used until after the first World War, decades into the future.

Skip to 2 minutes and 59 seconds Unfortunately, both Beatson and the referring surgeon agreed that nothing further could be done for this patient, in terms of surgery, to remove the cancer. However, she was willing to try anything that held out any prospect of a cure and gave permission for Beatson to try the highly experimental approach of removing her ovaries. She recovered well from the surgery. Within 18 months, there was no sign of cancer and she lived for a number of years afterwards. Following this remarkable success, Beatson undertook similar surgery in two more patients. Although the results were less striking, he was sufficiently encouraged by the results to present their case studies.

Skip to 3 minutes and 36 seconds The work was taken up by other surgeons and, within a few years, it was clear that the ovaries were the source of a factor that promoted breast cancer proliferation. And that interfering with this factor, at its source, could halt, or at least slow down, the progression of the cancer. This was a revolutionary idea at a time when cancer was widely thought to be parasitic in nature. And the idea of a factor secreted by one organ, that could act on another organ, was still very new. The term hormone wasn’t coined until 10 years after Beatson’s paper. And the ovarian hormones themselves, oestrogen and progesterone, were not isolated until 1930.

Skip to 4 minutes and 12 seconds The central principle of Beatson’s strategy for treating breast cancer, that is, interfering with the action of ovarian hormones, principally oestrogen, remains a mainstay of breast cancer treatment. The problem is that not all breast cancers respond. And for a long time, there was no way to tell who would likely benefit from the treatment and who would not. A major step forward came in the early 1970s, when a test that measured oestrogen receptor levels in breast cancer specimens was developed. And it became clear that the presence of oestrogen receptor predicted response to therapies that interfered with estrogen action. Oestrogen receptive testing is still an important factor in treatment decisions in breast cancer.

Skip to 4 minutes and 54 seconds At about the same time, compounds that competed with oestrogen for oestrogen receptor binding were being synthesised in various pharmaceutical companies, not as breast cancer therapies but rather as possible contraceptives. These compounds included Tamoxifen, which was ultimately shown to be a relatively nontoxic and effective therapy for breast cancer and has been used to treat millions of women worldwide. Without Beatson’s early work and the knowledge that interfering with oestrogen action could be used to treat breast cancer, Tamoxifen would never have been tested in this context.

Skip to 5 minutes and 28 seconds The combination of laboratory studies on its mechanism of action and the availability of a test for the presence of Tamoxifen’s target, the oestrogen receptor, meant that Tamoxifen could be directed to those most likely to benefit and used in a manner where it was most likely to be effective. So, Beatson’s work is important, not only because it led to a better treatment for breast cancer, but also because it reminds us that studying cancer biology, and how treatments work, can lead to better ways of treating cancer. You’ll hear about some more recent advances that have risen from a better understanding of cancer biology in other modules of this course.

The Beatson story

Dr Liz Musgrove looks back at the important work of Sir George Beatson in the 1890s.

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Cancer in the 21st Century: the Genomic Revolution

The University of Glasgow