Re­defin­ing cancer to re­duce un­nec­es­sary treat­ment

Modern Healthcare - - Q&A -

“We des­per­ately need a 21st century def­i­ni­tion of cancer ver­sus the 19th century def­i­ni­tion we’ve been us­ing.”

As chief med­i­cal of­fi­cer for the Amer­i­can Cancer So­ci­ety, seeks to Dr. Otis Braw­ley heighten pub­lic aware­ness about early de­tec­tion and preven­tion of cancer, the need for more re­search, and the ben­e­fits of smok­ing ces­sa­tion and di­etary im­prove­ments in re­duc­ing cancer deaths. He also works to elim­i­nate dis­par­i­ties in ac­cess to cancer care. Braw­ley is a pro­fes­sor of he­ma­tol­ogy, on­col­ogy, medicine and epi­demi­ol­ogy at Emory Univer­sity and is a mem­ber of the Cen­ters for Dis­ease Con­trol and Preven­tion ad­vi­sory com­mit­tee on breast cancer in young women. He pre­vi­ously served as as­sis­tant di­rec­tor of the Na­tional Cancer In­sti­tute. In his 2012 book, Braw­ley wrote about How We Do Harm, overtreat­ment and un­der­treat­ment of cancer pa­tients, as well as fi­nan­cial con­flicts of in­ter­est. Mod­ern Health­care re­porter Sabriya Rice re­cently spoke with him about how chang­ing the lan­guage and per­cep­tions sur­round­ing cancer could im­prove treat­ment. The fol­low­ing is an edited ex­cerpt.

Mod­ern Health­care: What is cancer?

Dr. Otis Braw­ley: Cancer is un­con­trolled cell growth. When a cell goes from one to two mi­to­sis, and then two to four, that’s usu­ally nor­mal growth. If there’s not a stop sig­nal, that’s when you have a cancer. The fact that people had these un­con­trolled growths is talked about in the Bi­ble and is even seen on the walls of caves in Egypt from 3,000 or 4,000 years ago.

MH: What do you think is prob­lem­atic about this def­i­ni­tion of cancer?

Braw­ley: We’ve used the biopsy a lot over the past 160 years, since the Ger­mans gave us the mi­cro­scopic def­i­ni­tion of cancer in the 19th century. They used au­top­sies of people who clearly died of breast, lung, colon and prostate can­cers. They were the first to do biop­sies and what we now call H&E stain­ing. They looked at biop­sies un­der their mi­cro­scopes, drew pic­tures of what they saw and de­fined what cancer looks like.

Now, 160 years later, keep in mind X-ray was in­vented in 1895, mam­mog­ra­phy in 1955, ul­tra­sound in the 1960s, CT in the ’70s, MRI in the ’80s, and some of our biopsy tech­niques have just been patented in the past 10 to 15 years. Now we can see a five-mil­lime­ter tu­mor in a woman’s breast, stick a nee­dle into the tu­mor, sam­ple it and send it to a pathol­o­gist. The pathol­o­gist uses the same H&E stain­ing tech­niques that were used 160 years ago and looks at it un­der a 2014 ver­sion of the mi­cro­scope. That pathol­o­gist says this looks just like what the Ger­mans de­fined as cancer 160 years ago.

The big dif­fer­ence is that what the Ger­mans saw was a tu­mor that clearly had spread and caused harm and killed the pa­tient. This 5 mil­lime­ter thing may very well not be ge­nom­i­cally or ge­net­i­cally pro­grammed to grow, spread and cause harm, and that’s what we call an over­diag­nosed cancer. In breast cancer, with mam­mog­ra­phy screen­ing, we be­lieve 10% to 30% of all of our lo­cal­ized can­cers are over­diag­nosed can­cers. These are women who will be treated need­lessly.

In prostate cancer, some people es­ti­mate 40% to 60% of prostate can­cers that we are cur­rently

di­ag­nos­ing are these over-di­ag­nosed can­cers. We des­per­ately need a 21st-century def­i­ni­tion of cancer ver­sus the 19th­cen­tury def­i­ni­tion we’ve been us­ing.

MH: What would that new def­i­ni­tion look like?

Braw­ley: I think it’s go­ing to be look­ing at spe­cific can­cers, and it’s go­ing be­yond look­ing at what the cancer looks like un­der the mi­cro­scope and ac­tu­ally look­ing into the genes. We’ve got some good leads.

We have a cou­ple of stud­ies and a cou­ple of tests that are avail­able now in breast cancer. They have not been per­fected yet. One looks at 21 dif­fer­ent genes in breast cancer and asks the ques­tion, “Is this spe­cific gene turned on or turned off? If it’s turned on, is it over­ex­pressed or not?” Ev­ery one of these 21 spe­cific genes is ex­am­ined and the same ques­tion is asked for each gene. And they ac­tu­ally say that some tu­mors tend never to be harm­ful, whereas other tu­mors al­ways seem to be ag­gres­sive. That’s mov­ing us al­ready to the point where we will say, “Ma’am, you have a cancer, but we’re go­ing to treat it less ag­gres­sively, be­cause our ge­nomic stud­ies in­di­cate that this may not be a very ag­gres­sive tu­mor.”

MH: Is that sim­i­lar to the case of duc­tal car­ci­noma in situ?

Braw­ley: DCIS is some­thing that looks like cancer, but it hasn’t pen­e­trated through the base­ment mem­brane. Most DCIS’ are in this over­diag­no­sis cat­e­gory. There are some DCIS’, es­pe­cially ones that we call high­grade DCIS’, that are des­tined to be­come in­va­sive can­cers later on.

I was al­ways taught when I took pathol­ogy that the term “in situ” es­sen­tially means “not.” It’s duc­tal car­ci­noma, but it has not in­vaded through the base­ment mem­brane. That’s what the “in situ” means. Un­for­tu­nately, many doc­tors, and es­pe­cially many pa­tients, when they hear duc­tal car­ci­noma in situ, they tend to get more con­cerned than per­haps they should, and they treat it like cancer. The amaz­ing thing is, to­day we have women who are get­ting bi­lat­eral mas­tec­tomies be­cause of duc­tal car­ci­noma in situ. But the same women, if di­ag­nosed with true breast cancer, would choose to get a lumpec­tomy and ra­di­a­tion—far less treat­ment for the real cancer.

MH: Last July, the Na­tional Cancer In­sti­tute pub­lished a

“I be­lieve if we can get a bet­ter def­i­ni­tion of real cancer, ver­sus some­thing that looks like cancer but ac­tu­ally will never cause harm, we can do a much bet­ter job for the pa­tient.”

paper propos­ing that the term “cancer” be re­served for le­sions with the like­li­hood of killing the pa­tient. Is DCIS an ex­am­ple where that type of def­i­ni­tion would be ap­pli­ca­ble?

Braw­ley: Duc­tal car­ci­noma in situ is such a fright­en­ing word, and it causes so much emo­tion on the part of doc­tors and pa­tients. Some ex­perts have said maybe we should take that fright­en­ing word car­ci­noma out of the phrase and in­stead call it an in­do­lent le­sion of un­de­ter­mined ori­gin.

MH: Would this kind of clar­i­fi­ca­tion help in terms of qual­ity of care and pa­tient safety?

Braw­ley: I be­lieve if we can get a bet­ter def­i­ni­tion of real cancer, ver­sus some­thing that looks like cancer but ac­tu­ally will never cause harm, we can do a much bet­ter job for the pa­tient. Ul­ti­mately, we’re go­ing to be able to tai­lor our care to the people who need the treat­ments ver­sus the people who don’t need the treat­ments. We’re closer to that in breast cancer than in any other dis­ease. The sec­ond cancer where we’re close is prostate cancer.

MH: When the NCI paper was pub­lished last year, crit­ics said this is just an­other way to deny care. What would you say to those people?

Braw­ley: It’s al­most im­pos­si­ble to com­bat state­ments that are that ig­no­rant, quite hon­estly. These are folks who hon­estly don’t un­der­stand medicine. I would much rather talk to the pop­u­la­tion that’s in­ter­ested in this ver­sus the pop­u­la­tion that’s try­ing to fan po­lit­i­cal flames.

MH: For cancer sur­vivors, what mes­sage would this send to them if we use the ter­mi­nol­ogy the au­thors rec­om­mended in that NCI paper?

Braw­ley: This is an im­por­tant ques­tion. In the prostate cancer lit­er­a­ture over the past two years, there have been at least a dozen pa­pers about whether Glea­son Score 5 and 6 prostate can­cers (scores in the mid-range on a 1-to-10 scale of what ex­perts be­lieve are tu­mors that will spread) should be called cancer.

Some of the people, as they an­swer these ques­tions in our med­i­cal jour­nals, say they don’t think we should change the name, be­cause we don’t want to tell half of the men who’ve been treated for prostate cancer over the past 50 years that a com­mit­tee has now de­cided that they didn’t have cancer. It is very, very tricky.

In his 2012 book, How

We Do Harm, Braw­ley wrote about overtreat­ment and un­der­treat­ment of cancer pa­tients, as well as fi­nan­cial con­flicts of in­ter­est.

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