15th Milan Breast Cancer Conference

Breast cancer treatment and prevention with tamoxifen and SERMS

Dr Andrea De Censi - E.O. Ospedale Galliera, Genova, Italy

Prevention of breast cancer there is a paradox: drugs that have been shown to be very effective, particularly tamoxifen and all these SERMs, which are selective oestrogen receptor modulators, have been shown to decrease by 40% breast cancer in total and by 50% oestrogen receptor positive breast cancer. So despite this strong evidence based on very large numbers of at least nine phase III double blind, very well conducted trials, the take-up by the medical community is very limited. We need to understand the reasons why cardiovascular medicine is twenty years above us in this regard with statins or anti-hypertensive drugs whereas in cancer we have very effective drugs, not only the SERMs or the aromatase inhibitors for breast cancer but aspirin at little dose for colorectal cancer and the pill, the oral contraceptive, for ovarian cancer. These are very effective interventions but the people don’t know and according to our survey the medical community doesn’t know too. So we still need to spread the notion that cancer can be prevented, of course with lifestyle changes such as diet or physical activity, but in at risk people, say 20% of the overall population, also with drugs.

Is this reduction in a healthy individual?

It is in healthy individuals and there are four trials with people at increased risk for family history, benign breast disease, late first pregnancy, early menarche. This is the composite risk assessment model by Gail. Five trials, though, were in osteoporotic women who are at lower risk from breast cancer because they have less oestrogen in the bone but also less stimulation for the breast. Yet the drugs, the SERMs, are very effective as well. So it’s very interesting because we have two different approaches from the cancer community take at risk women for breast cancer, from the osteoporotic community take women with osteoporosis. Because the SERMs have pleiotropic effects, oestrogenic on some organs like the bone or the vessels, the blood vessels, and anti-oestrogenic on the breast. So they are very interesting designer drugs.

Could this also be related to obesity?

Because of the aromatisation effect of adipose tissue which converts androgens produced by the adrenal cortex gland to oestrogens. So actually, yes, the lean women are at higher risk for osteoporosis. But the effect on breast cancer, the lower risk is even after adjustment for the body mass index.

You mentioned that a contraceptive pill might help prevent cervical cancer as well?

This is a very striking effect and it was published, say now, I guess five years ago in The Lancet and it’s one of the rare times that I read the editorial from the editor-in-chief and the editorial board which was a political editorial saying that it is a shame that this notion and the use of the pill is not widespread, given the lethality of ovarian cancer which is not as frequent as breast cancer but is a very lethal disease. Just with a few years of oral contraceptive you can prevent ovarian cancer. Now, it is used in the very high risk clinic who carry the mutation of the two genes, BRCA 1 and 2 because we know these women have a very high risk of ovarian cancer. You tend to give the pill because it’s more important to prevent ovarian cancer than breast cancer, even though you might increase the risk of breast cancer with the oral contraceptive. But Sara Gandini, who is just behind you but she is a shy scientist, has shown in a beautiful meta-analysis that with the new generation pills with lower hormone content you can still prevent ovarian cancer yet you don’t increase significantly the risk of breast cancer. So all in all it seems favourable to give the pill to prevent ovarian cancer without much concern about increased risk of breast cancer.

Are there any trials going on looking at aspirin in cancer?

Several. There is a huge study planned by the MRC in the UK which is called the Add-Aspirin trial. It is a study on over 10,000 patients with early colorectal or breast or prostate or gastro-oesophageal, these four, where they want to see if aspirin given in addition to the primary treatment, be it surgery or radiotherapy, chemotherapy and so forth, will reduce the risk of recurrence. This is based on the newer evidence from the cardiovascular trials where the emerging effect of aspirin is on cancer, not only cancer incidence as you might expect from the early data in colorectal polyps, but now also in the metastasis formations. So aspirin seems to be able to inhibit the formation of metastases and decrease the stage of disease and ultimately the mortality.

So we have, as well, we are about to launch the AIDA trial; Aida is the princess of Ethiopia, one of the most famous operas by Verdi. AIDA is Adjuvant Intervention with Daily Aspirin, where we will test the effect of aspirin on colorectal cancer after tumour surgery on top of chemotherapy. I am very enthusiastic of this idea. It’s still in the phase of getting funded because aspirin costs €1 per month, there’s very little commercial interest in these drugs. But it might be that our government is interested in this approach so I have spoken with the big authorities in Rome and I’m pretty optimistic. So there are these two trials, one in the UK and one in Italy, that should pursue the idea that aspirin can not only prevent cancer but also the consequences of cancer like the metastases.