In this segment, I'm going to talk about genetics as a tool in cancer prevention.

But to do that, I need to set the scene a little bit, and

talk about how cancer has been viewed described as the dread disease.

Cancer became increasingly prominent as a serious health concern in the early 20th

century as we begin to get control over infectious disease and, and

it was a source of great fear people didn't understand what caused it.

It was often incurable it was associated with painful lingering deaths and

therefore became in a very important focus of public health

efforts of something called the Anticancer Alliance,

a group of organizations that mounted campaigns for early detection.

The early detection focus was driven by a basic and what we now understand

to be somewhat over simplistic concept of cancer as a uniformly progressive disease.

The idea was that you had changes that were pre-cancer.

They led to cancer as a local disease.

After that there was regional spread.

And then wide metastasis.

So, with this idea of cancer in mind.

The idea was to define methods that allowed earlier and earlier detection.

In order to bring to bear very aggressive treatment to,

to stop the cancer and, and hopefully to cure it.

What also was a, a factor i, i,

in these early campaigns was a very a prominent focus on women.

As one scholar said, women have long been taught that cancer is

their special concern, and that, indeed, to worry about cancer is their duty.

The campaigns focused on women in several ways.

First of all, focused on overcoming natural modesty that

made women reluctant to undergo breast and pelvic exams.

Promoted screening, particularly the mammography and the pap test.

But also that women were expected to serve as, as, as one per,

person called it the private health officer for

the family, focusing on helping the whole family to be watchful,

to participate in screening and to hopefully detect any kind of cancer early.

So you can see a sort of historical and conceptual progression at work.

Originally as people first at the turn of the 20th century became much more

focused on cancer, what they were seeing was cancer often

being a problem that presented with a a symptom of distant metastasis.

So, in, in an example here using breast cancer a woman might

experience back pain and it turns out it's a metastasis from a breast cancer.

And that led to a focus on finding lumps, and

instructing women in self-exam with the idea that, that

they should bring to a doctors attention a lump and one could treat early.

And that led to the notion of routine exams, coming in to the doctor regularly,

so the doctor could examine and

perhaps find a lump even before the woman could find it herself.

That, of course,

moves on to mammography, finding early breast cancer that we can't even feel.

And in fact using the mammogram, not only to identify breast cancer,

but to identify early kind of pre-cancerous changes such as

something called Ductal Carcinoma In Situ not a true cancer.

But but in earlier earlier change so

this is the historical and conceptual progression that we saw during the 20th

Century, with an increasing emphasis on early cancer detection.

One of the outcomes of this focus on breast cancer screening,

was breast cancer anxiety.

Here's a quote from an article in a women's health magazine for many women,

it is as though the breasts themselves radiate anxiety.

One friend said recently, I don't have breasts anymore, I have time bombs.

and, and this demonstration,

this documentation of women's anxiety has come up a number of times.

i, in fact it may be that some of the media

presentation that was stimulated by the campaign may have stimulated that anxiety,

so here's just one example, this is a study that

asked the question how are breast cancer cases presented in the popular media?

And to what extinct do they compare or

differ from how breast cancer actually presents in the population?

And what the sta,

study was able to show, is that in a popular, high circulation magazines,

breast cancer tends to be presented, as a disease of young wo, women.

Stories emphasizing the consequence of cancer at a young age, thing

like the possibility of dying before ones children have grown, whereas the actually

reality in the population is that breasts cancer is, has a very different profile.

It's predominately a disease of older women not that,

that isn't obviously of great concern but its a little less scary than

presenting breast cancer as commonly occurring in the 30s an 40s.

Now, into this context of, of focus on early detection, focus on screening,

focus on a responsibility to find cancer early with a particularly and

emphasis on the role of women, comes advances in cancer genetics.

In the 1990s we began a dramatic era of gene discovery.

And there were two two areas of cancer where gene discovery was

particularly important two inherited forms of colon cancer were defined,

these were very rare conditions.

Where if we use genetic testing, we can identify people with an inherited risk,

who would identify, who, who would benefit from screening early in life.

And, we found the BRCA1 and BRCA2 genes.

Mutations in those genes are associated with a condition called

hereditary breast and ovarian cancer.

Which is a condition where we see families with early onset of breast cancer,

with both breasts and ovarian cancer.

And rapidly following those gene discoveries was the development of genetic

tests and these had the goal of identifying people who could benefit from

even more intensive screening than women in the general population were offered.

So, if we look at the her, historical and conceptual progression,

we can see that the notion of a DNA test to identify whether or

not you have a BRCA mutation fits right in.

So, we move from the early days where women might present with a bad symptom,

of a cancer that had spread to increasingly earlier detection and

now we have got the earliest detection of all.

The possibility of identifying a DNA test result that

tells us that a woman's at high risk for breast cancer.

She doesn't have breast cancer but she's at high risk for it.

So, let's think about using a DNA test, to identify whether or

not you're at high risk for breast cancer.

here's, here's the kind of situation we might have an individual who comes from

a family where we're strongly concerned about the possibility of genetic risk.

We see early onset breast cancer in the family,

we see ovarian cancer in the family and we say yes, BRCA testing,

because that can help us to determine whether or not early risk is present

in particularly the women that haven't yet had breast cancer or, or ovarian cancer.

What we have come to understand and it represents a very important limitation

on this model is that when we do this kind of testing a,

a fair amount of the time, we identify variants of uncertain significance.

so, the testing process involves assessing the DNA sequence of both the BRCA1 and

the BRCA2 genes.

Comparing those to a reference sequence,

a normal DNA sequence, and evaluating all fa variance.

There are three possibilities a person may be normal they may

either have exactly the same DNA sequence as the reference sequence or

they may have a change that we know is, is part of normal variation.

They may have a mutation associated with cancer risk, in which case we've

answered our question, or they may have a variant of unknown significance.

And these results are very confounding, they're difficult to deal with.

It's one of the prices we pay for

this kind of testing that it generates sometimes this kind of uncertainty.

Let's imagine though that what we have is a situation,

this is the same family I just showed you, in which we have identified the mutation.

so, we have the young women who had breast cancer at age 34, she under went testing,

we found a particular mutation in the BRCA1 gene, and then we tested her

sister who obviously is very concerned about the possibility of her own risk.

Her sister has a 50/50 chance, of inheriting the same risks and

and indeed we test her, and the sister is positive.

What are the options?

Well, the options are as we've already discussed the options are limited.

This th, the choices that we can offer this young woman are prim, primar,

primarily prophylactic surgery, meaning removal of the breasts to prevent

breast cancer, removal of the ovaries to prevent ovarian cancer or

intensive screening, screening every six months.

With both mammography and

breast MRI in order to see if we can detect a breast cancer early.

That screening obviously will not address the ovarian cancer risk.

So there are we have options and

they can help us to detect cancer early but they are limited options.

In fact, here's a comment there is a maddening dis,

disconnect between the cutting edge science of oncogenetics, and

what this commentator calls the barbaric state-of-the-art response to, d, d,

d, the discovery of a mutation hack off everything before it goes bad.

So, the options available to a woman with a BRCA mutation are limited.

We hope that those options will improve and get more sophisticated and

more precise.

But that's where we are now with this cancer susceptibility.

I now want to talk about probably the most famous person with a BRCA mutation,

Angelina Jolie.

This is her family as we gleaned from from the media.

She disclosed in an op-ed piece a few months ago that she has a BRCA mutation.

She described her family history,

which is clearly very consistent with this genetic risk.

Her mom died of ovarian cancer, and aunt died of breast cancer.

And she talked about having a preventive mastec, mastectomy.

And as she reflected on her preventive mastectomy and

her gratitude for having the opportunity to take that preventive step.

She also talked about how important it is for

women to have an option for, for genetic testing for breast cancer.

As she says, breast cancer alone kills some 458,000 people each year.

It has got to be a priority to ensure that more women can access gene testing and

life saving preventive treatment like what she herself was able to undergo.

But it's important to keep this in context,

clearly this was a very important and powerful story.

It received a lot of attention.

It was a very brave act on Angelina Jolie's part to talk about her personal

history but as one commentator says there was something she forgot to mention.

He proposed that there should have been a disclaimer in her story.

That actually, this story is not relevant to more than 99% of women.

As he says, there's no one right choice for a woman in Angelina Jolie's position,

but she may well have made the right choice for

her in, in choosing a preventive mastectomy.

Luckily, as he notes, it is a choice most women don't have to face.

In other words, genetics has been very powerful in

identifying a small proportion of women who have a high risk of breast cancer.

But we need to keep that in, in perspective and recognize that for

most women that kind of genetic risk is really not part of the picture.

Cancer Genetics: Genetics as a Tool in Cancer Prevention

Ethical and Social Challenges of Genomic and Precision Medicine

Meet the Instructors