Carcinoma of the Breast: Epidemiology

00:01 Welcome. In this talk we're going to discuss a very important entity Breast Cancer.

00:06 The epidemiology. It is the most common cancer in women.

00:10 One-in-eight women will develop cancer of the breast over the course of their lifetime.

00:17 If we take away all skin cancers because skin cancers overall are the most common cancers in women or men in the US or around the world.

00:26 If we take away the skin cancers, breast cancer constitutes about a third of all the noncutaneous malignancies.

00:34 Typically presents over the age of 40.

00:36 That's about 90% of cases.

00:38 Although, it is really common, just because one has breast cancer doesn't mean that one is going to die of breast cancer.

00:46 In the statistics currently with current therapies, and we are getting much better at treating breast cancer.

00:53 One out of 39 women who develop breast cancer will die from it.

00:57 Because it's so common that ends up making it the second most common cause of cancer deaths in the US.

01:03 And it's not just a disease or a cancer of women.

01:07 male breast cancer accounts for about 1% of the total cases of breast cancer overall.

01:12 The risk factors are largely hormonal.

01:14 Although there are some genetic risk factors as well as and we'll get into that.

01:18 It's estrogen being a growth factor.

01:21 So anything that gives prolonged periods of estrogen exposure or high levels of estrogen exposure will lead to an increased risk of developing breast cancer.

01:35 A high fat diet and obesity are associated with hyperestrogenic states.

01:41 Alcohol use, particularly because it especially with excessive alcohol use can lead to abnormal hepatic metabolism of estrogen can give you a hyperestrogenic state.

01:53 If you delay getting pregnant until much later, or have fewer pregnancies overall, that means you're at increased risk.

02:02 So, for example, a nun will be at higher risk of developing breast cancer than will a woman who has eight babies.

02:14 If you have an earlier menarche or a later menopause, so longer periods of time when you're having estrogen exposure will also increase your risk.

02:22 Smoking. Smoking increases the risk for a variety of malignancies.

02:26 A family history suggesting a genetic component.

02:29 And we know now that certain germline genetic mutations in BRCA1 and BRCA2, so called BRCA 1 and 2.

02:38 These are homologous recombination mismatch repair genes.

02:43 And p53, which is going to be the guardian of the genome responsible for identifying genetic abnormalities.

02:52 Those germline genetic mutations will influence risk.

02:56 We need to be aware that breast cancer is not created equal there are subtypes and increasingly because we recognize the different subtypes.

03:05 We can tailor therapy appropriately.

03:08 There are a number of pathways, two major ones.

03:10 But a number of pathways that drive breast epithelial proliferation.

03:14 One that we've already talked about is the estrogen pathway.

03:18 So estrogen binding to its receptor in the nucleus will drive a number of proliferative kind of pathways.

03:25 The second pathway involves the Human epidermal growth factor receptor 2, otherwise called HER2 or ERBB2, and when it's active a dimeric receptor on the surface of breast epithelium, that when epidermal growth factor binds to it can drive cellular proliferation through an independent pathway, not involving estrogens.

03:52 So, those are kind of two general flavors of proliferative pathways that we need to be concerned about when we're thinking about breast cancer.

04:02 Overall, there are three major groups.

04:03 So there's going to be an Estrogen Receptor-positive breast cancer, where the major driver is estrogen. Those will tend to be HER2.

04:13 So, epidermal growth factor receptor 2-negative.

04:16 Usually also, if epithelium is estrogen responsive, it's also going to be progesterone responsive. And in some cases, progesterone may be a driver of epithelium proliferation as well.

04:30 The ER-positive, HER2-negative cancers represent a little over 50% of breast cancers.

04:37 Then there are the HER2-positive.

04:39 So, an upregulation of the HER2 receptor will lead to activation of that particular pathway.

04:48 These tumors were there is upregulation of HER2 estrogen and progesterone receptor, positive or negative, that's not too important, but it's recognizing the increased expression of the HER2 receptor.

05:01 And these involve 10% to 20% of breast cancers.

05:04 And then there are the so called Triple negative breast cancers.

05:07 These tend to have the worst prognosis overall.

05:10 They’re estrogen receptor-negative, progesterone receptor-negative, and HER2-negative.

05:15 They are being driven by other pathways.

05:19 And as they say they have a much worse prognosis, they represent 10% to 20% of cancers.

05:25 And we'll come back to each of these in turn.

05:27 This is just to give you kind of a sense of the relative numbers of the different kinds of the three flavors of breast cancer and when they start becoming apparent.

05:38 And so we had said most of the breast cancers occur over the age of 40, and that's represented on this curve.

05:44 Estrogen receptor-positive, HER2-negative tumors are the most common. And you see that as a top curve.

05:53 The estrogen receptor positive or negative, but HER2-positive tumors are the purple line and the estrogen receptor-negative tumors have about the same kind of overall incidence and timeline of development.

06:08 Breast cancers arise in kind of the two different cell types that lined the ducts and the lobules.

06:15 And to understand kind of the designation that we're going to see later on in lobular carcinoma or ductal carcinoma, you have to think about this.

06:24 There are the cuboidal epithelial cells that sit nearest the lumen.

06:29 and these have an epithelial phenotype. Sitting just beneath them, and these have an epithelial phenotype. Sitting just beneath them, And both of these cells are lying on top of the basement membrane.

06:38 But beneath the superficial epithelial cells are myoepithelial cells.

06:43 These are cells that have a little bit of smooth muscle like behavior, and a little bit of epithelial like behavior.

06:49 And you can get cancers that arise in either the epithelial cells that's most common, or in the myoepithelial cells.

06:56 And again, they can occur in the lobules, out in the part of the breast, where we're going to be forming milk or they can form in the ducts.

07:05 And that is going to be the the main avenues by which the lobular secretions reach the nipple.

07:13 Okay for research trials, and increasingly you may see this in your day to day care of patients we’ll refer to patients not necessarily as HER-2/neu positive or all those things, but we'll talk about them being luminal, HER2-enriched, and basal-like.

07:30 The Luminal A type tumors are epithelial.

07:34 They tend to be relatively low grade.

07:36 They're going to be ER-positive. They're also usually PR-positive.

07:39 So, estrogen receptor and progesterone receptor positive.

07:42 And they're going to be HER2-negative cancers, Driven predominantly, by responsiveness to estrogens.

07:50 The Luminal B type tumors are epithelial.

07:53 They tend to be higher grade.

07:55 They're going to be ER and PR positive.

07:57 And they may be HER2-positive.

08:00 But the difference between Luminal A and Luminal B are the additional mutations that have occurred and we go from a lower grade, more indolent tumor to a higher grade, more aggressive tumor.

08:11 There are the HER2-enriched tumors.

08:15 These are epithelial tumors, not the myoepithelium.

08:18 Epithelium, they overexpressed the HER2-receptor.

08:22 They tend to be estrogen and progesterone receptor negative.

08:26 And then there are the basal-like.

08:27 So these are going to be the cells that are the myoepithelial layer.

08:32 And the cells in that region, are ER and PR-negative and HER2-negative And as I've said previously, the ER-negative, PR-negative, HER2-negative, triple-negative tumors in this designation basal-like are the most aggressive.