Latest / Get Real with Jim Weiss / Dr. Laura Esserman and Dr. Steve Birrell (Pioneering Androgen Therapies for Breast Cancer & Should All Breast Cancers Be Called Cancer?)

Transcript

Dr. Laura Esserman and Dr. Steve Birrell (Pioneering Androgen Therapies for Breast Cancer & Should All Breast Cancers Be Called Cancer?) · Get Real with Jim Weiss

• 0:09
  Speaker 1: I'm Jim Weiss, chairman and founder of Real Chemistry, and
• 0:12
  Speaker 1: this is the Get Real with the Chairman podcast. Hey everyone,
• 0:21
  Speaker 1: Today I'm speaking with doctors Laura Essermon and Steve Burrell.
• 0:25
  Speaker 1: They're working together to change the breast cancer treatment paradigm.
• 0:28
  Speaker 1: Doctor Esserman is a force of nature in breast cancer
• 0:32
  Speaker 1: and in cancer in general. Since nineteen ninety three, she's
• 0:35
  Speaker 1: worked at UCSF as a surgeon and oncology specialist and
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  Speaker 1: co lead of their Breast Oncology program. She's gained an
• 0:43
  Speaker 1: audience by publishing over four hundred peer reviewed articles and
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  Speaker 1: appearing in mainstream news, most recently The New York Times,
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  Speaker 1: where she published a provocative editorial this summer on whether
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  Speaker 1: doctor carcinoma and C two otherwise known as DCIS, should
• 0:59
  Speaker 1: be called answer at All. In twenty sixteen, she was
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  Speaker 1: named one of Time Magazine's one hundred most Influential People.
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  Speaker 1: She was also a member of President Obama's Council Advisors
• 1:11
  Speaker 1: on Science and Technology, where she developed channels for federal
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  Speaker 1: support the science based medical innovation. She's joined today by
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  Speaker 1: the incomparable doctor Steve Burrell, founder of Hava Therapeutics based
• 1:23
  Speaker 1: in Adelaide Australia of OZ developing a potentially revolutionary testosterone
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  Speaker 1: based approach to the treatment of breast cancer.
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  Speaker 2: Steve's three decade career in cancer.
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  Speaker 1: Spans many roles as a specialist, a surgeon, a medical innovator,
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  Speaker 1: and one of the most widely published molecular oncologists. The
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  Speaker 1: two are collaborating right now on an ice by trial
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  Speaker 1: reevaluating the treatment of DCIS. Together, we'll talk about the
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  Speaker 1: context and rationale for this trial and the science as
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  Speaker 1: we learn about them and how their passions outside of
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  Speaker 1: their research fueled their commitment to innovation.
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  Speaker 2: For now, tune into our inspiring chat.
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  Speaker 1: I'll just say, first of all, thanks so much for
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  Speaker 1: doing the podcast.
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  Speaker 2: Really really appreciate it. Thanks for doing this.
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  Speaker 1: I'd certainly like to get into all the details of
• 2:17
  Speaker 1: the thing you two are collaborating on, which is the
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  Speaker 1: icepy trial, But before that, I just wanted to set
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  Speaker 1: the stage and say, how'd you guys first get together?
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  Speaker 2: How'd you' all meet? Like, how do you know each other?
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  Speaker 2: What is the.
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  Speaker 1: History maybe in terms of what each of you were
• 2:32
  Speaker 1: doing and how your paths crossed, and then continue across.
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  Speaker 2: I'll start with you Laura.
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  Speaker 3: Trying to remember when I first met you, Steve.
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  Speaker 4: I think I met you at a meeting in either
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  Speaker 4: sit Ne or Melbourne, and it was something that it
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  Speaker 4: was Melbourne and I was working You were wanting to
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  Speaker 4: do something on Granulumnus mass titus that I had that
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  Speaker 4: my fellow Rachel was working on, and part of that
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  Speaker 4: density workshop that Bruce had me.
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  Speaker 3: Give some long talk on whatever.
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  Speaker 4: Anyway, I think that you know, we're both interested in
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  Speaker 4: a different approach to breast cancer prevention. I think that
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  Speaker 4: there has been really too little attention on the science
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  Speaker 4: of prevention or an approach that actually reduces the incidents
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  Speaker 4: of breast cancer and the risk of lethal breast cancer.
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  Speaker 4: And there's so much focus on once you're diagnosed what
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  Speaker 4: to do about it, and the chronic treatment of metastatic
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  Speaker 4: disease without trying to take the lessons of biology and
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  Speaker 4: take a step back and say, oh, well, wait a minute,
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  Speaker 4: why aren't we developing the science prevention. I think a
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  Speaker 4: lot of people think it's impossible, but of course things
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  Speaker 4: are only impossible if you make it so. Then I
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  Speaker 4: think there was this connection over agigen receptors, and I
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  Speaker 4: think both Wayne and Steve have this very novel approach.
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  Speaker 4: But interestingly, Steve and I, both from a clinical since
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  Speaker 4: I think it's stumbled on this idea. I mean, I've
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  Speaker 4: been using MRI as a an intermediate biomarker in all
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  Speaker 4: my trials since the mid nine since working with Nola Hilton,
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  Speaker 4: who actually developed the sequences for MRI. I think that
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  Speaker 4: imaging is a catalyst for change, and sometimes when you
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  Speaker 4: want to make a change, you have to have something
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  Speaker 4: that people can.
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  Speaker 3: Picture and see.
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  Speaker 4: That's the different And it just so happens that Steve
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  Speaker 4: and I were sort of using this kind of background
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  Speaker 4: enhancement and sort of different ways of sort of thinking
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  Speaker 4: about it and also thinking about DCIS not as a
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  Speaker 4: cancer but as an opportunity for prevention. And there's not
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  Speaker 4: really that many of us who have been thinking about
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  Speaker 4: that because it's not quite the normal dogma, although it's
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  Speaker 4: obviously the most rational way to approach it. But I
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  Speaker 4: think we bonded over that it was such an unusual
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  Speaker 4: approach that I decided I had to go visit them
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  Speaker 4: kind to make sure they weren't totally crazy. I mean,
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  Speaker 4: it's okay to be crazy as long as you're the
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  Speaker 4: good kind of crazy. Anyway, so I decided to go
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  Speaker 4: over to Adelaide and meet up with them.
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  Speaker 5: At all, well very much so that way.
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  Speaker 6: I think that what struck me about Laura is she
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  Speaker 6: reminded me very very much of my mentor, who was
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  Speaker 6: the first female surgeon in South Australia, who was the
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  Speaker 6: first breast cancer surgeon in Australia, and who mentored me
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  Speaker 6: through my very early career, including mentoring Wayne Tilly, who
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  Speaker 6: is my long term collaborator.
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  Speaker 5: Her name was Liz Cant.
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  Speaker 6: She's no longer with us, but she nominated and anointed
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  Speaker 6: me to take over her position. And so when I
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  Speaker 6: actually met Laura, it struck me that she had the
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  Speaker 6: same drive and the questioning of the paradigm which Liz had,
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  Speaker 6: and is synchronized with me significantly because, as Laura said,
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  Speaker 6: most of breast cancer development has been at the end
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  Speaker 6: stage of the disease working backwards. And the first trial
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  Speaker 6: I ever did was a prevention study with timoxifen, and
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  Speaker 6: everyone thought I was crazy to go into it, but
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  Speaker 6: I thought, well, we're.
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  Speaker 5: Deal with the wrong end of the disease.
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  Speaker 6: We need to go back to the beginning and it
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  Speaker 6: might be difficult, but we need to find the answer
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  Speaker 6: that which will also inform usis to how to deal
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  Speaker 6: with the.
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  Speaker 5: Other end of the disease, which proved to be the case.
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  Speaker 6: So I've really have been taken by Laura and I
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  Speaker 6: spy program.
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  Speaker 4: And then we decided then they were going to go
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  Speaker 4: to San Antonio, and I talked to them coming to
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  Speaker 4: San Francisco instead, and we did this JOYT Prostate and
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  Speaker 4: Breast cancer program looking at androgen receptors. You know, people
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  Speaker 4: have a window into the way they look at things
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  Speaker 4: and they think that's the universe. So we and breast
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  Speaker 4: cancer we're looking at a particular way, and the prostate
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  Speaker 4: cancer people were looking a particular way. But at the
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  Speaker 4: end of the day, we're learning and thinking, oh, we
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  Speaker 4: both were looking at it differently, and there's so much
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  Speaker 4: you can learn from each other. I think this is
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  Speaker 4: the good thing about out of the box thinking. It's
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  Speaker 4: not really out of the box thinking, it's really taking
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  Speaker 4: a step back. Sometimes people just sort of get so
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  Speaker 4: much into the details, they're so into the weeds that
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  Speaker 4: they can't take a step back and say, Okay, what's
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  Speaker 4: the big picture here. So we're looking at estrogen receptor
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  Speaker 4: and progester receptor. But actually there's estrogen receptor, progester receptor,
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  Speaker 4: androgen receptor, and local corticoid receptors. That's the family of
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  Speaker 4: steroid receptors that are all involved. And the prostay cancer
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  Speaker 4: people have been doing this work for two or three decades.
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  Speaker 4: I mean plenty that we can learn there, and plenty
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  Speaker 4: that we can learn from the two or three decades
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  Speaker 4: that we've taken from telescoping in in a slightly different
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  Speaker 4: version on the estrogen side of things, But none of
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  Speaker 4: us have the complete picture.
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  Speaker 3: And I think Donald McDonald sort of had the best look.
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  Speaker 3: He said, well, all.
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  Speaker 4: Of us should just learn the lesson and start with
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  Speaker 4: ingrogen receptor agonism and here's why. And so I was
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  Speaker 4: really struck by this, and I thought, well, yeah, why
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  Speaker 4: not try it? And I'd love to try it in
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  Speaker 4: stage two three breast cancer the neolagpen setting. But it's
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  Speaker 4: such a departure for people. Sometimes you have to think
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  Speaker 4: about where's the easiest place to do it.
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  Speaker 3: The easiest place to do.
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  Speaker 4: It actually is dcis because there's a growing group of
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  Speaker 4: us are like so tired of dealing with this entity
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  Speaker 4: and treating it like cancer. It's just so inane to
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  Speaker 4: keep doing the same thing over and over again and
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  Speaker 4: somehow hoping that we're going to do better. Why not
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  Speaker 4: try it there because if it works there, I'm in
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  Speaker 4: my phase one and two trials and dcis they're going
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  Speaker 4: to go on to invasive cancer. So it's start of
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  Speaker 4: starting in the metastatics setting. You know. Now we're starting
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  Speaker 4: in the prevention side and moving inwards. There's lots of
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  Speaker 4: ways to learn, and it's so important to keep your
• 8:18
  Speaker 4: mind open, especially where you can test new ideas where
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  Speaker 4: you're going to do no harm and in fact you're
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  Speaker 4: much more likely to bring about benefit. You know. I've
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  Speaker 4: been working on this into since two thousand and eight.
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  Speaker 4: Two thousand and nine I published with Ian Thompson, who's
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  Speaker 4: a very prominent urologist Press Stay cancer surgeon on rethinking screening.
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  Speaker 4: We actually originally wanted to call the article screening for
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  Speaker 4: breast and prostate cancer. Is it the best of times
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  Speaker 4: or the worst of times? Jamison mere Jamma. We don't
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  Speaker 4: do cute, but in fact that is really story. The
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  Speaker 4: story is we've embarked on this huge screening program in
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  Speaker 4: the hopes that we would do good. But you have
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  Speaker 4: to take a step back in say sometimes the baby's ugly,
• 9:02
  Speaker 4: you have to admit where you've made a mistake. Now,
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  Speaker 4: it's very interesting in the prostate cancer community, people understand
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  Speaker 4: that there's harm from screening, The interventions have a mortality rate,
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  Speaker 4: the interventions have long term consequences. Well, in fact, that's
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  Speaker 4: true for breast cancer as well. People just didn't realize it.
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  Speaker 4: And I think it's also that before we started screening
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  Speaker 4: for breast cancer, the majority of breast cancers were more
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  Speaker 4: lethal cancers.
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  Speaker 3: So people just.
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  Speaker 4: Didn't realize that as we started screening and finding this
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  Speaker 4: reservoir of more indolent disease, that we were sort of
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  Speaker 4: diluting the pool, and many of these just weren't that serious,
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  Speaker 4: and that led us to overtreatment. So overdiagnosis is less
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  Speaker 4: of a problem if you can recognize it immediately and
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  Speaker 4: do something different. And we called in twenty thirteen for
• 9:48
  Speaker 4: a nomenclature change and caused a big star and then
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  Speaker 4: it kind of went away. And I think when Scott
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  Speaker 4: Igner contacted me again and said, well, let's let's write
• 9:57
  Speaker 4: it af ED and I said, well, okay, Because I
• 10:00
  Speaker 4: had participated in a meeting on Gleason six and It
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  Speaker 4: was so interesting. The pathologists really were the ones against it,
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  Speaker 4: and they're saying, well, we're afraid of causing harm. We're like, well,
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  Speaker 4: you're already causing harm. You are the ones causing harm.
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  Speaker 4: I mean, there's great data and prostate cancer that over
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  Speaker 4: diagnosis and overtreatment is harmful, and I think it's just
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  Speaker 4: people just not recognizing it.
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  Speaker 3: And I think that, you know, people say, well, what's
• 10:25
  Speaker 3: wrong with calling it cancer?
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  Speaker 4: I said, because when you hear the word cancer, people think,
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  Speaker 4: oh my god, I'm going to die tomorrow, and if
• 10:30
  Speaker 4: I don't do something aggressive, I'm going to die.
• 10:34
  Speaker 3: But you have to ask yourself what exactly are these entities?
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  Speaker 4: So instead of taking the usual approach of just cut
• 10:42
  Speaker 4: it out, take an approach and say, wow, what if
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  Speaker 4: this is a window into understanding how to prevent disease.
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  Speaker 4: When you take something and you turn panic and emergency
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  Speaker 4: into it, people can't think, and people are like frightened
• 10:56
  Speaker 4: and they just want to do everything scorched earth. That's
• 10:58
  Speaker 4: why twenty five thirty percent of people have bilateral mess
• 11:01
  Speaker 4: ectomy after gcis, which in my book is like ridiculous.
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  Speaker 4: Sometimes it's indicated, but why not try something first it's
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  Speaker 4: not unlike what we've done with the whole ICEPY program,
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  Speaker 4: which is you're diagnosed with a big cancer, don't start
• 11:15
  Speaker 4: with surgery.
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  Speaker 3: Okay, I'm a surgeon. I know this.
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  Speaker 4: If you are at risk for a fast growing, aggressive
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  Speaker 4: cancer and your big risk is systemic recurrence, it's not
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  Speaker 4: the breast, but the breast is the canary in the cage,
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  Speaker 4: get the treatment right.
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  Speaker 2: And stay there. Because I think listeners will understand this.
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  Speaker 2: We were kind of.
• 11:33
  Speaker 1: An Angelina Joli era now Olivia mine recently was diagnosed.
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  Speaker 1: And when we see this, if the public tends to
• 11:41
  Speaker 1: react with, like you said, panic or fear and God
• 11:45
  Speaker 1: are going aggressive?
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  Speaker 2: Is this more of an argument for what you're saying.
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  Speaker 4: Yes, certainly people misunderstood the whole Angelina Jolie and never
• 11:53
  Speaker 4: like it was like, oh my gosh, everyone should have
• 11:54
  Speaker 4: a biledal mess ect me by no means, Angelina Jolie
• 11:58
  Speaker 4: had an inherited mutation brack of one, no question, a
• 12:03
  Speaker 4: risk factor for hormone receptor negative tumors, okay, where you
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  Speaker 4: have a eighty five percent likelihood over the course of
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  Speaker 4: your life.
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  Speaker 5: To have that.
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  Speaker 4: She made a choice that she didn't want that risk
• 12:15
  Speaker 4: you can. Surgery in that case is ninety five percent
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  Speaker 4: risk producing. Hopefully in the next few years we'll have
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  Speaker 4: a treatment for those cancers that's much less aggressive where
• 12:22
  Speaker 4: people won't have to do that, but we don't have
• 12:24
  Speaker 4: it yet.
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  Speaker 6: Well, the Olivia Mum story is interesting because she's raised
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  Speaker 6: the spectrum of luminal bee cancer. But one of the
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  Speaker 6: things that came across with the following, well, I looked
• 12:35
  Speaker 6: at her. She was forty one when she had her
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  Speaker 6: first child. That's a significant risk factor for developing breast cancer.
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  Speaker 6: They didn't mention in the risk factor that her breastidency,
• 12:46
  Speaker 6: which is the number one.
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  Speaker 5: Risk factor for reast disease.
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  Speaker 6: But the fact that she got luminal be hormonly says
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  Speaker 6: toive breast cancer.
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  Speaker 5: That is the cancer I mentioned.
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  Speaker 6: Which has got the highest risk of hormone resistance, which
• 13:01
  Speaker 6: we are targeting with T plus AI therapy. So the
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  Speaker 6: first trial in the advance from the T plus AI
• 13:08
  Speaker 6: in as a therapeutic in advanced breast cancer or in
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  Speaker 6: the ice by trial outside of DCIS will be in
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  Speaker 6: the luminal B category where there are no good therapeutics
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  Speaker 6: right now.
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  Speaker 5: And the big thing about hormonal.
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  Speaker 6: Treatment is that it's becoming more and more targeted. But
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  Speaker 6: the problem with targeted therapy in hormonal disease is that
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  Speaker 6: it is linked to the global hormonal action within the
• 13:37
  Speaker 6: woman's body. You can't isolate it from the global effects.
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  Speaker 6: And that's why we're not trying to. We're actually utilizing
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  Speaker 6: a target of the androgen receptor, but at the same
• 13:51
  Speaker 6: time allowing it off target effects which are naturally endemic
• 13:56
  Speaker 6: within the woman to enhance their life and quality of life.
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  Speaker 6: And that's effect which is I think we need to
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  Speaker 6: take more note of, much more note.
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  Speaker 4: Now. This is a DCIS trial that we're working on.
• 14:08
  Speaker 4: This is the wast station. DCIS is. Absolutely you are
• 14:12
  Speaker 4: at high risk for developing a breast cancer. So if
• 14:15
  Speaker 4: we find, for example, that this TESTASRUM plus AI technique
• 14:18
  Speaker 4: really works, we can translate that immediately into wisdom and say, oh,
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  Speaker 4: let's look for the people at highest risk for developing
• 14:28
  Speaker 4: hormone driven tumors and make that one of the options
• 14:32
  Speaker 4: for risk reduction.
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  Speaker 3: This is like a window both to treatment and to prevention.
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  Speaker 4: We have this study in it's twenty twenty four, right.
• 14:43
  Speaker 4: The BRCA one gene was cloned in nineteen ninety six,
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  Speaker 4: bracket two in nineteen ninety seven.
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  Speaker 3: It's almost twenty years.
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  Speaker 4: We should at the very least be looking for goodness sakes,
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  Speaker 4: there are nine genes twelve genes actually that.
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  Speaker 3: Increase people risk. It's not very common, two.
• 15:02
  Speaker 4: To three percent, but we should at least, at the
• 15:06
  Speaker 4: very least be identifying those people. There are lots of
• 15:09
  Speaker 4: other things polygenic risk, small variations in the genes that
• 15:14
  Speaker 4: predict risk, PRS, polymeny gene risk where we can add
• 15:18
  Speaker 4: to that, plus all the other tools that we have
• 15:21
  Speaker 4: on models, including breast density and Steve and I can
• 15:25
  Speaker 4: tell you some of the breast density or enhancement on
• 15:29
  Speaker 4: MR can serve as intermediate markers to help us say,
• 15:32
  Speaker 4: how are we doing with that risk reduction. Part of
• 15:35
  Speaker 4: the reason why risk reduction has not worked in breast
• 15:38
  Speaker 4: cancer is we don't have these intermediate markers. Think about
• 15:42
  Speaker 4: hypertension and heart disease, Think about cholesterol and heart disease.
• 15:46
  Speaker 4: People can measure cholesterol, they can measure your blood pressure,
• 15:50
  Speaker 4: they can look at weight, They can look at all
• 15:51
  Speaker 4: of these things and see are my tools working. This
• 15:55
  Speaker 4: has been one of the big blocks. You know, women
• 15:57
  Speaker 4: don't want to take things that don't work. They don't
• 16:00
  Speaker 4: want to just take things blindly and have no idea
• 16:02
  Speaker 4: whether they work. So what we're trying to do is
• 16:05
  Speaker 4: develop these intermediate markers that tell us, first of all,
• 16:08
  Speaker 4: are you at risk? Second of all, can we see
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  Speaker 4: something that's an expression of risk, like background enhancement or
• 16:14
  Speaker 4: un MARI that we can measure and say.
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  Speaker 3: Is it working? Is it going away?
• 16:18
  Speaker 4: So this is the crux of a lot of what
• 16:21
  Speaker 4: we're doing, and that's what the recast DCIS trial is about.
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  Speaker 4: It's really what all the ice by trials are have
• 16:26
  Speaker 4: in common, but it's you've got to develop the suite
• 16:29
  Speaker 4: of tools to make prevention a real discipline.
• 16:33
  Speaker 1: What would you say is one thing people misunderstand that
• 16:36
  Speaker 1: you hope this will clarify.
• 16:38
  Speaker 6: Tests OSRA and DCIS are grossly misunderstood in a generic sense. One,
• 16:46
  Speaker 6: most women don't know that they've got lots of testosterone.
• 16:50
  Speaker 6: They don't know how it is an a natural ability
• 16:53
  Speaker 6: to actually overcome esogenic activity.
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  Speaker 5: That's a really important educational tool. So most women do
• 17:00
  Speaker 5: not want.
• 17:01
  Speaker 6: To look like me, but to look like me, you
• 17:03
  Speaker 6: need to have lots and lots of testosterone compared to estrogen.
• 17:08
  Speaker 6: And so the subtlety of there is the delivery, which
• 17:11
  Speaker 6: is what we've you know, Harve's doing.
• 17:13
  Speaker 5: The second thing is that we have an opportunity.
• 17:16
  Speaker 6: To re educate on the risk of inside you cancer
• 17:23
  Speaker 6: or carcinoma, potentially change its name to like what happened
• 17:29
  Speaker 6: with an abnormal spear test, cervical smear test to a
• 17:33
  Speaker 6: tippy or or give it different types of names so
• 17:36
  Speaker 6: that people are not invoked into an immediate panic response.
• 17:40
  Speaker 1: Yeah, so tell us, like how you made a shift
• 17:44
  Speaker 1: out of oncology surgery to founding to breast cancer Research
• 17:49
  Speaker 1: cent Arizan, creating Havah and getting into.
• 17:52
  Speaker 5: Where we are.
• 17:52
  Speaker 2: Can you bring us to where we are moving now
• 17:56
  Speaker 2: with your partnership.
• 17:58
  Speaker 6: As an academic, you can spend your academic career generating
• 18:02
  Speaker 6: lots of publications, but if you don't actually have material
• 18:06
  Speaker 6: impact on outcome of disease, and I think you've failed
• 18:09
  Speaker 6: yourself and the people who've supported you. And to that end,
• 18:14
  Speaker 6: I think the generation of intellectual property via commercialization is
• 18:19
  Speaker 6: absolutely critical. If you don't get it out there, it's
• 18:23
  Speaker 6: not going to have an impact. And it became quite
• 18:27
  Speaker 6: clear to me that if you are not going to
• 18:29
  Speaker 6: engage in a paradigm shifting alteration in therapeutics, you need
• 18:36
  Speaker 6: to get out there and collect around you people like
• 18:40
  Speaker 6: Laura who are prepared to see a different direction. And
• 18:46
  Speaker 6: when I ran the breast cancer clinics, which are some
• 18:48
  Speaker 6: of the largest in Australia, it became quite clear to
• 18:51
  Speaker 6: me that no one was actually looking at this complex
• 18:55
  Speaker 6: interface between female foremones and breastase. There were not clinics
• 19:01
  Speaker 6: that specialized in that concept. And so that's why I
• 19:05
  Speaker 6: established clinics that actually specialized in hormones and breast disease,
• 19:09
  Speaker 6: because the too are so interrelated. And I just want
• 19:13
  Speaker 6: to digress with slightly on that point, because I have
• 19:16
  Speaker 6: a very provocative lecture in Oxford just before Christmas and
• 19:20
  Speaker 6: titled one hundred and thirty years have we gone in
• 19:23
  Speaker 6: the wrong direction?
• 19:24
  Speaker 5: And what that pertained to was the fact that one
• 19:28
  Speaker 5: hundred and thirty years.
• 19:29
  Speaker 6: Ago a guy called George Beatson took out a young
• 19:31
  Speaker 6: woman's ovaries who had metastatic breast cancer and invoked a
• 19:36
  Speaker 6: significant pathological remission. And it then set the paradigm for
• 19:43
  Speaker 6: the next one hundred and thirty years, which removing estrogen
• 19:47
  Speaker 6: was the only way to deal with breast cancer. But
• 19:50
  Speaker 6: what that invoked were two things. As Laura spoke to,
• 19:54
  Speaker 6: it invoked a significant degradation of a woman's essential formonal components,
• 20:01
  Speaker 6: which are.
• 20:01
  Speaker 5: Critical to their well being into the future.
• 20:04
  Speaker 6: Now, when you're dealing in an esthetic setting like that,
• 20:08
  Speaker 6: it's a no brain it's a cost benefit analysis.
• 20:10
  Speaker 5: You know, the benefit outraid the cost.
• 20:13
  Speaker 6: But as Laura alluded to, as the disease has got
• 20:15
  Speaker 6: earlier and earlier, we've translated those same sledge hammer type
• 20:21
  Speaker 6: approaches to the management of early stage disease. And this
• 20:26
  Speaker 6: is when I formed Harbor because I thought, well, if
• 20:31
  Speaker 6: we're going to go down a pathway like this, I
• 20:33
  Speaker 6: need a vehicle that I can take out and shop around.
• 20:36
  Speaker 6: And I think that it's culminated in dc as. But
• 20:40
  Speaker 6: one of the really exciting things for me is a
• 20:44
  Speaker 6: being in Asia, which Australia is. We're in close proximity
• 20:47
  Speaker 6: to China, and next week I'm going up to the
• 20:50
  Speaker 6: Milk and Institute Seminar on Global Investment and involved in
• 20:55
  Speaker 6: a round table discussion on the catastrophic nature of the
• 21:00
  Speaker 6: increase in breast cancer mainland China that's occurring. The reason
• 21:04
  Speaker 6: that that is important is that it opens up an
• 21:08
  Speaker 6: avenue to the largest collection of women in the world
• 21:13
  Speaker 6: of a similar ethnic background who are undergoing a sociological
• 21:17
  Speaker 6: demographic alteration of urban to rural existence, which in the
• 21:24
  Speaker 6: presence of ultra high breast density which Chinese women tend
• 21:28
  Speaker 6: to have, and how you deal with that when the
• 21:32
  Speaker 6: disease in China is different in that the age of
• 21:36
  Speaker 6: average agon set is forty four. That means that fifty
• 21:40
  Speaker 6: all under forty four, So you're actually getting into a
• 21:43
  Speaker 6: very young age group. And alluding to what Laura said
• 21:48
  Speaker 6: on the blood pressure cuff of the breast, I believe
• 21:52
  Speaker 6: is MRI, and what I'm going to advocate for is
• 21:56
  Speaker 6: MRIs screening with artificial intelligence READOUBT and potentially preimaging hormonal
• 22:04
  Speaker 6: manipulation of the breast tissue to reduce the metabolic background
• 22:08
  Speaker 6: so you get better vision. In order to do this,
• 22:11
  Speaker 6: you need people of vision who are capable of seeing
• 22:15
  Speaker 6: the magnitude of what is being advocated. I think there
• 22:19
  Speaker 6: are people of vision around this sort of topic.
• 22:23
  Speaker 5: That's why you know this.
• 22:24
  Speaker 6: This Milk and Institute first meeting in there's a US
• 22:28
  Speaker 6: China meeting in Hong Kong's It's going to be really
• 22:31
  Speaker 6: exciting because it brings together the genesis of breast cancer,
• 22:35
  Speaker 6: the opportunity for screening, opportunity for prevention, and the health
• 22:40
  Speaker 6: economics of breast cancer.
• 22:42
  Speaker 5: Cost is going to be massive.
• 22:43
  Speaker 6: In China has gone up to thirty four percent in
• 22:46
  Speaker 6: the last decade.
• 22:47
  Speaker 5: The instance of breast cancer.
• 22:48
  Speaker 4: Well, the good news they're going to have to come
• 22:50
  Speaker 4: up with cheaper, faster, better screen techniques and you know,
• 22:54
  Speaker 4: diffusion weighted imaging could be extremely cheap, absolutely.
• 22:58
  Speaker 3: Doing fast ultra fast.
• 23:00
  Speaker 4: Them are changing some of the techniques to making them cheaper, faster, better,
• 23:04
  Speaker 4: But again, the health economics of screening will be completely
• 23:07
  Speaker 4: unaffordable unless we think about who needs what. The majority
• 23:11
  Speaker 4: of women are not at risk for breast cancer, even
• 23:14
  Speaker 4: though it's an extremely common disease, even if it's one
• 23:17
  Speaker 4: in eight, that means seven out of eight don't get it.
• 23:20
  Speaker 4: So being able to tailor who to put your resources
• 23:25
  Speaker 4: into is huge and China will absolutely have to do that.
• 23:29
  Speaker 4: I mean, there's no way they can afford these big
• 23:31
  Speaker 4: screening programs that in my opinion, pretty wasteful. You have
• 23:35
  Speaker 4: to think about how to tailor what you're doing. The
• 23:39
  Speaker 4: science of risk assessment has to progress and then you
• 23:43
  Speaker 4: also have to be as we said from two thousand
• 23:45
  Speaker 4: and nine one, you have to understand what is the
• 23:47
  Speaker 4: consequence of screening and how do you deal with what
• 23:50
  Speaker 4: you find. And I think that over time, how people
• 23:54
  Speaker 4: responded to the editorial that we wrote this summer in
• 23:57
  Speaker 4: the New York Times, Well, I think there's the online
• 24:00
  Speaker 4: comments and the comments that I got in my email.
• 24:03
  Speaker 4: There are the people who aren't threatened by any change,
• 24:07
  Speaker 4: and then the people who have been dealing with this
• 24:09
  Speaker 4: for so long, thanking us for talking about it and
• 24:14
  Speaker 4: putting it out there.
• 24:15
  Speaker 5: One thing, which just to pick up on.
• 24:16
  Speaker 6: What Laura has said years ago, I was talking in
• 24:20
  Speaker 6: I think it was Columbia University, and I was giving
• 24:22
  Speaker 6: a public lecture and there was a woman who looked
• 24:25
  Speaker 6: very familiar during the front row, and I just couldn't
• 24:28
  Speaker 6: place her. And she got up at the end and
• 24:31
  Speaker 6: she made a very interesting question statement, and she said,
• 24:35
  Speaker 6: the problem with you doctors, there's always a bad way
• 24:38
  Speaker 6: to start the problem with you doctors, especially male doctors,
• 24:41
  Speaker 6: is that you use fear to cultivate your own bias
• 24:45
  Speaker 6: and your relationship in your female patients. And I thought
• 24:51
  Speaker 6: long and hard about that, and she was absolutely right.
• 24:55
  Speaker 6: It was Gloria Steinem and she's absolutely right in that
• 25:00
  Speaker 6: many codes have got their personal bias and by nature
• 25:05
  Speaker 6: conservative because they don't want to do harm. But within
• 25:11
  Speaker 6: that is a very strong lever that they can use
• 25:16
  Speaker 6: to bias a patient towards their own direction. And I'm
• 25:20
  Speaker 6: not saying it's intentional, it's just embedded in the DNA
• 25:25
  Speaker 6: of medical practice. And one of the most important things
• 25:30
  Speaker 6: about what Laura and are doing and also Jim, what
• 25:34
  Speaker 6: you're doing is communication to medical practitioners about this alteration
• 25:40
  Speaker 6: in the dynamic and so that we can change the
• 25:45
  Speaker 6: bias towards a different way of thinking and acceptance, which
• 25:48
  Speaker 6: is this is not a marketing tool. It's an essential
• 25:53
  Speaker 6: component of education that the women are asking for more
• 25:58
  Speaker 6: options and we need to educate the midi cos as
• 26:02
  Speaker 6: to why we're thinking what we're thinking. We're we're not crazy.
• 26:06
  Speaker 6: We do this a long time, and we're trying to
• 26:09
  Speaker 6: present a new option and do it utilizing the scientific
• 26:14
  Speaker 6: method but challenging the paradigm, and that's always going to
• 26:18
  Speaker 6: be tricky.
• 26:19
  Speaker 2: Well, I experienced some of this. I do think it's
• 26:22
  Speaker 2: possible to do this.
• 26:23
  Speaker 1: I worked with anthotype DX and Genomic Health on the
• 26:27
  Speaker 1: tailor our ex trial that changed the paradigm somewhat on
• 26:31
  Speaker 1: what one does completely in recurrence right and after that
• 26:37
  Speaker 1: initial treatment. But it sounds like that you want to
• 26:39
  Speaker 1: move further up that stream because so many people are
• 26:44
  Speaker 1: diagnosed and we haven't reduced things, So we don't even
• 26:47
  Speaker 1: want to get to that.
• 26:48
  Speaker 4: Point where we're not thinking about what's bringing down the
• 26:51
  Speaker 4: incidence of breast cancer. And so DCIS is absolutely a
• 26:55
  Speaker 4: consequence of screening, and because it kind of looks under
• 26:58
  Speaker 4: the microscope like answer, we've just lumped it all in
• 27:02
  Speaker 4: and then we're treating it. And I think women when
• 27:04
  Speaker 4: they read about it are very confused. They're like, Okay,
• 27:07
  Speaker 4: why is this the only option I've given? And a
• 27:10
  Speaker 4: lot of people are recommended to have a mess ectomy
• 27:12
  Speaker 4: and they're like, WHOA, why should I do this? And
• 27:15
  Speaker 4: I've had people in my office weeping. Can you imagine
• 27:17
  Speaker 4: someone said why not just cut them off? And you
• 27:19
  Speaker 4: just get a new set as if that was like nothing.
• 27:24
  Speaker 4: The customer is your patient, And like people say, well,
• 27:26
  Speaker 4: why do you want to change?
• 27:27
  Speaker 3: I said, because last I checked.
• 27:29
  Speaker 4: And when I offer options and I sit across the
• 27:31
  Speaker 4: table from someone No one says, oh fantastic, I love that.
• 27:34
  Speaker 3: I'll choose that.
• 27:42
  Speaker 1: Now I want to shift into a section I'm calling
• 27:45
  Speaker 1: so what's it all mean? Where we hear about your
• 27:47
  Speaker 1: work and action and how it's playing out in the
• 27:49
  Speaker 1: real world.
• 27:55
  Speaker 2: So test sauserone, it just sounds like.
• 27:59
  Speaker 4: Really for yeah, yeah, well we're not you know again,
• 28:02
  Speaker 4: We're not giving it at a dose where people are
• 28:04
  Speaker 4: going to grow a beard and be punching out their neighbors,
• 28:07
  Speaker 4: not interested in turning them into mail aggressors.
• 28:10
  Speaker 3: That's not it.
• 28:10
  Speaker 4: It's and Steve can go into the details, but if
• 28:14
  Speaker 4: you you know again, it turns out that testosterone, if
• 28:18
  Speaker 4: it's processed properly, can be one of the most profound
• 28:22
  Speaker 4: inhibitors of estrogen signaling in the breast. You're doing the
• 28:27
  Speaker 4: right thing biologically to shut down the things that may
• 28:31
  Speaker 4: be promoting the outstanding growth of these cancers. And if
• 28:34
  Speaker 4: you think about the one time in the US where
• 28:38
  Speaker 4: we significantly dropped the incidence of breast cancer was the
• 28:42
  Speaker 4: Women's Health Initiative Study. When the announcement came out that
• 28:45
  Speaker 4: combined estrogen and progesterone increase with the risk of breast
• 28:50
  Speaker 4: cancer by twenty five percent and not just little bit decancers,
• 28:54
  Speaker 4: but aggressive cancers. The sale of combined hormone replacement dropped
• 28:59
  Speaker 4: and the incidents dropped, So this is a cautionary This
• 29:04
  Speaker 4: is such an important message that there are things that
• 29:08
  Speaker 4: we can do, we just have to be more serious
• 29:10
  Speaker 4: about it.
• 29:10
  Speaker 6: I think in that that HRT story is critically important
• 29:14
  Speaker 6: because the HRT combination that was utilized was estrogen which
• 29:20
  Speaker 6: was generated from pregnant horse heurone combined with a synthetic progesterone,
• 29:27
  Speaker 6: which that combination was potentially or significantly damaging to breast
• 29:33
  Speaker 6: tissue because of its synthetic and very unnatural combination. We
• 29:38
  Speaker 6: know that now with HRT, if you're using natural estrogen,
• 29:42
  Speaker 6: estradil and natural progesterone and natural testosterone, that they don't
• 29:48
  Speaker 6: have the same off target effects, which is I think
• 29:52
  Speaker 6: a really important observation because women were scared off from
• 29:56
  Speaker 6: HRT in and live in misery as a result of
• 29:59
  Speaker 6: those results, and.
• 30:00
  Speaker 4: FEEA not everybody in misery, And I would say, I
• 30:03
  Speaker 4: think that there are things that we can do where
• 30:05
  Speaker 4: we don't have We don't have to get into that.
• 30:07
  Speaker 4: But like estrogen alone was not particularly a culprit the
• 30:10
  Speaker 4: Women's Health Initiative. We have a lot of data on that,
• 30:14
  Speaker 4: and Steve and Wayne have data that even a very
• 30:17
  Speaker 4: small amount of testosterone, as long as you give the
• 30:20
  Speaker 4: room tase and hibter, just as a way to make
• 30:22
  Speaker 4: sure that you're pushing the biology so that people make
• 30:26
  Speaker 4: dihydro testosterone, which is profoundly suppressive to the estrogen stimulation
• 30:33
  Speaker 4: of cells, which can reduce your risk. But the great
• 30:37
  Speaker 4: thing about it is it's associated with well being, and
• 30:41
  Speaker 4: you know, it doesn't reduce your libido, and it doesn't
• 30:44
  Speaker 4: cause vaginal joyness, and it doesn't you know, it's it's
• 30:47
  Speaker 4: really at low enough doses that it's very tolerable. I
• 30:51
  Speaker 4: feel like the paradigm for people to understand is heart disease.
• 30:55
  Speaker 4: When I started practice, your chance of dying of heart
• 30:59
  Speaker 4: disease is and was double that of dying of cancer.
• 31:02
  Speaker 3: That's no longer true.
• 31:03
  Speaker 4: And it's no longer true because people have taken a
• 31:07
  Speaker 4: systematic look, starting from the Framingham study to try and
• 31:09
  Speaker 4: understand what are the factors that drive and heart disease risk,
• 31:13
  Speaker 4: blood pressure, lack of exercise. Then people started developing tools
• 31:18
  Speaker 4: to reduce that risk.
• 31:19
  Speaker 2: But Steve, why don't you tell us for this I
• 31:22
  Speaker 2: spy recast trial about how long are we away from
• 31:25
  Speaker 2: an answer here and what would if all things go ideally,
• 31:30
  Speaker 2: will this trial show.
• 31:32
  Speaker 6: Well, it's a very short runway on the trial because
• 31:35
  Speaker 6: we have such a rapid output of a reading, which
• 31:38
  Speaker 6: is MRI change in the breast and so three months,
• 31:42
  Speaker 6: six months, MRI recruitment over the next eighteen months to
• 31:45
  Speaker 6: two years, and hopefully the results to be coming out
• 31:48
  Speaker 6: shortly after that. Having such an accurate tool as MRI
• 31:52
  Speaker 6: and having people like Nola Hilton being engaged in utilizing
• 31:57
  Speaker 6: this tool, I'm pretty confident that we'll get a fitty
• 32:00
  Speaker 6: rapid result. I think that the big thing for me
• 32:04
  Speaker 6: is that. And as a Laura very wisely approached this issue.
• 32:09
  Speaker 6: She approached it at the front end of the disease
• 32:13
  Speaker 6: rather than going into the more complex breast cancer. The
• 32:18
  Speaker 6: most complex breast cancer is hormonally resistant disease, and it
• 32:23
  Speaker 6: is the greatest cause of breast cancer mortality, and that
• 32:28
  Speaker 6: is the natural extension for many reasons for this therapeutic.
• 32:33
  Speaker 6: But going into the front end, like I have a
• 32:36
  Speaker 6: Laura going into the front end, which I did with
• 32:38
  Speaker 6: Charles the prinzy the Mayo. Looking at side effects profiles
• 32:42
  Speaker 6: and breast cancer patients is the way to socialize the
• 32:45
  Speaker 6: concept and get proof of concept to vasty indication of
• 32:50
  Speaker 6: the medication.
• 32:52
  Speaker 5: But there is one thing which I really I think
• 32:54
  Speaker 5: is critically important.
• 32:55
  Speaker 6: My belief is that breast cancer actually starts at a
• 32:58
  Speaker 6: very very young age or the procliviency to the genesis
• 33:02
  Speaker 6: of breast cancer, and if you're actually doing pure prevention,
• 33:07
  Speaker 6: you need to look at a younger age group. Premenopausal
• 33:10
  Speaker 6: women who have got menstrual cycles have significantly more ovarian
• 33:15
  Speaker 6: produced estrogen, which trying to block out that estrogenic activity
• 33:20
  Speaker 6: in the breast is much more complex than in a
• 33:22
  Speaker 6: postmenopausal breasts.
• 33:24
  Speaker 5: And so that's why this paradigm is.
• 33:26
  Speaker 6: So important and intriguingly, our friend Sarmon not down Cticyani
• 33:32
  Speaker 6: did a paper on transgender men utilizing testosterone and examining
• 33:37
  Speaker 6: the breast tissue and comparing it with pre impost menopausal
• 33:40
  Speaker 6: women breast tissue, and they have mystectomies, and the testosterone
• 33:44
  Speaker 6: had profound effect on the carcinogenic nature of breast tissue
• 33:50
  Speaker 6: by reducing inflammation, altering a significant immunomodulation, and even though
• 33:56
  Speaker 6: the dosing is significantly higher, it is a proof of
• 33:59
  Speaker 6: con sip that utilizing this pathway is very efficacious.
• 34:04
  Speaker 5: Men do have brisk issue, but breast cancer min is rare.
• 34:07
  Speaker 4: If you have brack a one or two mutation, the
• 34:09
  Speaker 4: timetone know about it is in your thirties before half
• 34:13
  Speaker 4: the caners arise. And so these are things that we
• 34:17
  Speaker 4: know about. And if we can start figuring out what
• 34:20
  Speaker 4: the proclivities are, and if we can take and marry
• 34:23
  Speaker 4: these risk factors to fast growing cancers or slow growing
• 34:28
  Speaker 4: cancers and we can start to match the risk reducing interventions,
• 34:33
  Speaker 4: then we can start to make a significant dent. Here's
• 34:36
  Speaker 4: what we know about breast cancer, breast cancer subtypes and
• 34:39
  Speaker 4: what will reduce risk. Here's what we know about trials
• 34:42
  Speaker 4: with early interventions. Here's what we know about birth control,
• 34:46
  Speaker 4: cycle control, postpartum weaning, et cetera, et cetera. How can
• 34:50
  Speaker 4: we start thinking about all the things that we're already doing.
• 34:53
  Speaker 5: And Lord, that's critically important.
• 34:55
  Speaker 6: You know, the hormone of contraception is a critically important
• 34:59
  Speaker 6: factor in how we manage this. And Noora and I
• 35:02
  Speaker 6: have talked about the potential of putting an engigen into
• 35:06
  Speaker 6: a oural contraceptive because the traditional oural contraception completely obliterates
• 35:13
  Speaker 6: the level of testostra and has a significant effect on
• 35:16
  Speaker 6: brist issue.
• 35:17
  Speaker 4: So Steve, we're going to give it a word for
• 35:19
  Speaker 4: the best ideas. We're going to have a shark tank
• 35:21
  Speaker 4: a competition at the end, so you should apply absolutely.
• 35:24
  Speaker 1: So Mary I had asked Steve, like, if this recast
• 35:27
  Speaker 1: trial is successful.
• 35:28
  Speaker 2: What will it show us and then where do we
• 35:30
  Speaker 2: go from there?
• 35:31
  Speaker 4: Okay, So there are three key things that this recast
• 35:35
  Speaker 4: trial will show. Number One, that it's feasible to take
• 35:39
  Speaker 4: a six month window, assess risk at the beginning of
• 35:42
  Speaker 4: that six months, and reassess at the end of six months.
• 35:45
  Speaker 3: That's a safe approach.
• 35:47
  Speaker 4: That too, that the changes that we see will be
• 35:50
  Speaker 4: extremely predictive of your future risk of developing breast cancer
• 35:55
  Speaker 4: and the change and that reassessment at six months can
• 35:59
  Speaker 4: be an early endpoint for risk reduction. That I would
• 36:04
  Speaker 4: say could be an early endpoint for accelerator to approval
• 36:08
  Speaker 4: from the FDA. Then the third thing is we are
• 36:12
  Speaker 4: going to characterize every single dcis and as well as
• 36:18
  Speaker 4: the person who gets it so that we can understand
• 36:21
  Speaker 4: the germline risk or the inherited risk, so that we
• 36:25
  Speaker 4: can understand the milieu and the immune environment, so that
• 36:29
  Speaker 4: we can understand the nuance and the type of DCIS
• 36:33
  Speaker 4: that people get, so we can do a better job
• 36:35
  Speaker 4: of understanding which treatments work for which kinds of dcis,
• 36:40
  Speaker 4: and were are the opportunities where some of these new
• 36:43
  Speaker 4: agents are better than our standard treatments because they address
• 36:47
  Speaker 4: the biology differently and because they're more tolerable. That's the
• 36:51
  Speaker 4: way to win. That's the way to advance the actual
• 36:55
  Speaker 4: treatment of dcis. But in fact it's bigger than that.
• 36:58
  Speaker 4: It's about how to advance science of prevention.
• 37:01
  Speaker 1: And do you think there'd be more study required after
• 37:04
  Speaker 1: or could we really in a couple of years change
• 37:06
  Speaker 1: this paradigm.
• 37:07
  Speaker 4: I think it depends how well we meet our three
• 37:11
  Speaker 4: year risk prediction, but I think if we do, and
• 37:15
  Speaker 4: it's very clear in our registry trial, there's a group
• 37:18
  Speaker 4: of people at a fifty to sixty percent risk of
• 37:20
  Speaker 4: developing a cancer in the next over the three to
• 37:22
  Speaker 4: four years versus ten percent, and ten percent is what
• 37:26
  Speaker 4: we see after lumpectomy and radiation and arma therapy so like,
• 37:31
  Speaker 4: if you can get that same risk reduction with just
• 37:36
  Speaker 4: the medication, why would you add the surgery radiation? I
• 37:39
  Speaker 4: mean because I think part of the problem with DCIA
• 37:41
  Speaker 4: says is it a risk factor or is it really
• 37:44
  Speaker 4: a focal marker that you're going to develop cancer?
• 37:46
  Speaker 3: Right there?
• 37:47
  Speaker 4: I think most of them are not focal markers that
• 37:50
  Speaker 4: cancer is going to develop. I think they're just risk factors,
• 37:53
  Speaker 4: and so you have to learn how to treat them differently.
• 37:56
  Speaker 3: And just like any good trial, it's a hypothesis.
• 37:59
  Speaker 4: If I didn't think I was right, like no one
• 38:02
  Speaker 4: would follow me, but I wouldn't do the trial.
• 38:04
  Speaker 3: But it's pretty logical.
• 38:05
  Speaker 4: Our data is pretty compelling, it's published, and so if
• 38:09
  Speaker 4: that's true, why not use this as a paradigm to
• 38:12
  Speaker 4: change people's lives, change people's options, change the whole treatment
• 38:16
  Speaker 4: for DCIS and the paradigm for prevention.
• 38:21
  Speaker 6: I think the most important thing that Laura has said
• 38:25
  Speaker 6: is that change in paradigm, that the rapid introduction of
• 38:30
  Speaker 6: a new direction, utilizing her unique trial system to get
• 38:36
  Speaker 6: accelerated approval with post approval registry analysis is a safe
• 38:42
  Speaker 6: way of going forward and it makes it a lot
• 38:46
  Speaker 6: easier for investors and people coming behind the program to
• 38:52
  Speaker 6: know that they don't have to wait for twenty years
• 38:55
  Speaker 6: like we did with tomoxifen or thirty years it talk
• 38:58
  Speaker 6: to actually get it through. So it's really an important
• 39:02
  Speaker 6: way of getting into the market utilizing acceptable ways of trialing.
• 39:09
  Speaker 5: And she's been very successful.
• 39:11
  Speaker 2: Your approach has been used in a lot of patients,
• 39:13
  Speaker 2: and it really it's something that maybe we've overlooked. I
• 39:17
  Speaker 2: think at least what a thousand patients have taken this
• 39:21
  Speaker 2: combination and have had good outcome and it's been safe
• 39:26
  Speaker 2: or at least while tolerated, so it's not like we're
• 39:30
  Speaker 2: it's almost as if a large phase one has been done.
• 39:33
  Speaker 6: And that's a really it's a really important point because
• 39:37
  Speaker 6: utilizing to recognized compounds, combining them and using them off
• 39:42
  Speaker 6: label in this way is challenging to people because it
• 39:47
  Speaker 6: is an out of the box approach. I was encouraged
• 39:49
  Speaker 6: years ago by Barry Marshall, who won the Nobel Prize
• 39:53
  Speaker 6: for discovering that the heat to go back to caused
• 39:55
  Speaker 6: Barry I was saying, I was saying to Barry that
• 39:58
  Speaker 6: I'm getting a lot of the heat from people over
• 40:02
  Speaker 6: trying to change a paradigm, and he said, you've got
• 40:05
  Speaker 6: no idea what I got when I said that ulcers
• 40:09
  Speaker 6: are caused by bacteria, because there was so much pressure
• 40:15
  Speaker 6: from people with bias over the having your stomach removed
• 40:20
  Speaker 6: was still the answer. And this is the equivalent of that.
• 40:24
  Speaker 6: And this is what Laura's saying. You don't need to
• 40:27
  Speaker 6: have your breast removed, just like you don't need to
• 40:30
  Speaker 6: have your stomach removed. These are big things, and you
• 40:34
  Speaker 6: come up again against a lot of competing forces, including
• 40:37
  Speaker 6: an inherent bas so you know, we do have the experience.
• 40:40
  Speaker 5: There are phase two be.
• 40:43
  Speaker 6: Really it was a phase three trial we did the
• 40:45
  Speaker 6: Mayo Clinic was very important, and that was placebo control
• 40:48
  Speaker 6: demonstrating that plus AI really significantly improved quality of life
• 40:53
  Speaker 6: for breast cancer patients, which is it encourages them to
• 40:57
  Speaker 6: keep taking their medication. And that's part of the corollary
• 41:01
  Speaker 6: here is that utilizing T plus AI as an add
• 41:05
  Speaker 6: on to current therapeutics to enhance their quality of life
• 41:10
  Speaker 6: potentially enhance the efficacy of the medication.
• 41:14
  Speaker 5: And the compliance issue is a really huge thing.
• 41:18
  Speaker 6: They estimate thirty to forty percent of women stop their
• 41:20
  Speaker 6: medication because of side effects.
• 41:22
  Speaker 5: And never tell the doctor.
• 41:23
  Speaker 6: They're too embarrassed or they just don't want to go
• 41:25
  Speaker 6: into that they stop it.
• 41:27
  Speaker 2: Yeah, you mentioned that we're successful here. We should certainly
• 41:31
  Speaker 2: learn of the potential new treatment and paradigm sooner versus later.
• 41:37
  Speaker 2: That's really the takeaway.
• 41:39
  Speaker 6: I think that coming in on DCIS is a really
• 41:42
  Speaker 6: well it comes to the front end of the disease,
• 41:45
  Speaker 6: and so it gives us a window of opportunity to
• 41:47
  Speaker 6: do two things. One is to better enhance the way
• 41:51
  Speaker 6: we treat advanced cancer by under better understanding of response
• 41:56
  Speaker 6: to these therapeutics, but also gives an opportunity of prime prevention.
• 42:01
  Speaker 5: Of the disease.
• 42:01
  Speaker 6: So it's a by phasic action, which that's why it
• 42:05
  Speaker 6: makes it such a powerful trial. I think that coming
• 42:08
  Speaker 6: back to this the problem in China, I know that
• 42:12
  Speaker 6: when we start screening high risk people, we are going
• 42:15
  Speaker 6: to find bucket loads of DCIS. I mean seven hundred
• 42:20
  Speaker 6: million women when you focus down with a one child policy,
• 42:25
  Speaker 6: with ultra breast density, with urbanization, which we know results
• 42:29
  Speaker 6: in increased risk of developing breast cancer. There's no strategy
• 42:33
  Speaker 6: in place to be able to deal with this. And
• 42:36
  Speaker 6: I have a friend who runs a breast cancer hospital
• 42:38
  Speaker 6: in Beijing. He operates seven days a week from six
• 42:41
  Speaker 6: a m. Till midnight, and he still can't stay on
• 42:44
  Speaker 6: top of the problem. And we have a window of
• 42:47
  Speaker 6: opportunity to actually make a significant impact.
• 42:49
  Speaker 1: Well, we're going to keep checking back in with you
• 42:51
  Speaker 1: as this study and your work progresses. And I think
• 42:55
  Speaker 1: actually where you're going, I think the community wants to
• 42:59
  Speaker 1: go there with you.
• 43:00
  Speaker 3: They do if we just need a little more courage.
• 43:02
  Speaker 4: Yep, and Steve and I are not afraid anyway.
• 43:07
  Speaker 2: Thanks again so much. This was an inspiring conversation. Thank you,
• 43:12
  Speaker 2: Hey everyone, thanks for listening in today.
• 43:14
  Speaker 1: The Get Real with the Chairman podcast is a production
• 43:17
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• 43:20
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• 43:25
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• 43:29
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  Speaker 1: and we'll see you on the road.