Dr. Anton Titov, MD.: Professor Lippman, you mentioned that the prevention of up to 70% of all breast cancers could happen with anti-hormonal therapies. Could you please discuss more strategies to prevent breast cancer at the age of precision medicine? Certainly, it's not so much precision here because 100% of men or women will grow breasts before puberty if you give them estrogens. So it's nothing precise. Estrogens can stimulate about It's obvious. Because that's the case, it's also been clear from all kinds of epidemiology studies that women who have a later onset of puberty have a much lower risk of breast cancer. This has been known for decades. For example, a woman whose period starts at age 16 has about 1/3 of the risk of breast cancer of a woman whose periods started at age 12. Isn't that amazing? Four years difference has that big effect on breast cancer risk multiple decades later. And as people have gotten bigger, from birth onwards, since height and weight control the onset of puberty, the onset of puberty in the United States is age 10. So there's no question that longer exposure to hormones increases the risk of breast cancer. It's just one of the reasons why western world women have much higher risks of breast cancer than people who lived in Asia in the previous century. Their breast cancer risk was women living in the West. And as western lifestyle has swept over the world, we have seen gigantic increases in the risk of breast cancer. Because this is so clear, because we understand that these hormonal factors can strongly influence breast cancer, we know that women who have premature menopause have a lower risk of breast cancer. It became obvious when we had drugs that could interfere with estrogen action to try them in breast cancer prevention trials. And those studies have been done involving multiple countries and involving 10s of 1000s of women. And for example, using a drug called tamoxifen, women who are on an intent to treat basis will prescribe Tamoxifen for five years. Not all of them took it. Dr. Marc Lippman, MD.: But if you compare the women who were prescribed Tamoxifen for five years, compared to women who didn't take it, they had about a That's extraordinary. It is extraordinary! And of course, as I've just gotten through saying, easily a third of those women didn't even take the pills for the five years. Similar studies have been done with other drugs which interfere with hormone action, so-called aromatase inhibitors. These drugs block the conversion of androgen precursors produced by the adrenal glands to estrogens. These are very potent drugs, mostly for postmenopausal women. And in studies using those drugs, easily with five years of use of those drugs. So they're extremely effective. The problem is that many women are afraid to use them. And many physicians are afraid to prescribe them because many of these drugs have been labeled as having serious side effects. The fact is that in randomized, double-blind trials in which women cannot tell whether they're getting placebo, or Tamoxifen, or placebo or an aromatase inhibitor, the overwhelming majority of women cannot successfully identify whether they're on the drug treatment or the placebo. So the most common side effect of one of these drugs is nothing. It's nothing. And therefore even, there's no reason not to try them. You would notice side effects if you have them. People don't like if they feel hot flashes. They don't feel right or something. If it occurs, stop the drug, no harm, no foul. Dr. Marc Lippman, MD.: But most women would take these drugs and they have no side effects whatsoever. They will reduce the risk of breast cancer by 75%. It seems kind of silly not to try them, don't you think? Absolutely. So it's a question of just inertia in clinical practice. Well, it's also because the other problem, of course here it is this. It's one thing to treat someone with cancer, patients with cancer. It's a horrible diagnosis, people are willing to suffer tremendous side effects. Dr. Marc Lippman, MD.: But if you are well, and you are dealing with the statistical risk reduction, you don't want to have any side effects. So a lot of literature, lots of garbage, frankly, that's on the internet, have scared people away from doing things that under most circumstances are harmless. Aromatase inhibitors are not associated with any important organ system toxicities. No heart, no liver, no kidney, no lung toxicities. There's no leukemia. They're not toxic drugs. They can have subjective side effects in some women. Dr. Marc Lippman, MD.: But I repeat, the most common side effect is nothing.