Win­ning the war on Breast Can­cer ...a progress report

Wellness Update - - Breast Cancer -

Over the past 30 years, “the pink rib­bon” has be­come syn­ony­mous with breast can­cer and the fight to “find a cure”. Find­ing a cure means preven­tion, early de­tec­tion and treat­ment of breast can­cer and more sur­vivors.

In spite of ap­prox­i­mately 39,520 breast can­cer deaths in 2012, sec­ond only to lung can­cer, there is great progress be­ing made, es­pe­cially in the later and more deadly stages of the disease.

Aware­ness ef­forts have cer­tainly led to an ear­lier di­ag­no­sis for many, but we haven’t been able to reach the ul­ti­mate goal—a cure. For pa­tients in the ad­vanced stages of breast can­cer such as Stage IV or metastatic, they too of­ten feel aban­doned or left out of the fight. But ac­cord­ing to physi­cians like Dr. Mar­i­ana Chavez-MacGre­gor, As­sis­tant Pro­fes­sor at the Breast Med­i­cal On­col­ogy De­part­ment at The Univer­sity of Texas MD An­der­son Can­cer Cen­ter, the fight for ad­vanced stage can­cer pa­tients is be­com­ing more ag­gres­sive than ever – with more wins seem­ingly ev­ery day.

In the United States, ap­prox­i­mately 40,000 women and 500 men die ev­ery year from Metastatic Breast Can­cer (MBC). Metastatic, or Stage IV is when breast can­cer has spread to other parts of the body, in­clud­ing or­gans like the liver, lung, bones and oth­ers. The chal­lenge is to stop the spread and ex­tend the life ex­pectancy of the pa­tient. That means find­ing a drug that tar­gets the can­cer. Eas­ier said than done.

Ac­cord­ing to the Na­tional Foun­da­tion for Can­cer Re­search (NFCR), “breast can­cer is most likely to be­come fa­tal when can­cer­ous cells metas­ta­size, or spread, to other parts of the body. In fact, more than 90% of can­cer mor­tal­i­ties are due to can­cer that has metas­ta­sized. Even af­ter suc­cess­ful re­moval of a pri­mary tu­mor, can­cer pa­tients still live un­der the con­stant fear that a few can­cer cells have es­caped the surgery, and th­ese cells may even­tu­ally be­come sec­ondary tu­mors in other lo­ca­tions of the body.

“We are look­ing at new drugs that act dif­fer­ently than stan­dard chemo­ther­apy – we know them as ‘tar­geted ther­a­pies’ and they usu­ally act in a spe­cific path­way. We are try­ing to un­der­stand and iden­tify those tar­gets. We are try­ing to iden­tify the high­way in­side the cell that has been iden­ti­fied as a prob­lem so we can treat that can­cer cell with a spe­cific tar­geted ther­apy di­rected to re­vert the course in that high­way.”

The key to sur­vival or even ex­tended life ex­pectancy for ad­vanced can­cer is to find ef­fec­tive drugs that can tar­get the path­ways and stop the spread. It’s sur­pris­ing – and re­fresh­ing – to re­al­ize how much ef­fort is go­ing into re­search. At MD An­der­son Can­cer Cen­ter alone, Dr. Chavez-MacGre­gor said, more than 100 drugs (or com­pounds) are un­der re­search as part of clin­i­cal tri­als for dif­fer­ent tu­mor types at any given time. Hap­pily, the re­search some times (I wish it more of­ten) turns out a lit­tle more hope.

Metastatic can­cer pa­tients can be on med­i­ca­tions for the rest of their life. Once the can­cer has spread to other parts of the body, treat­ments can slow down or stop the spread. But as a gen­eral rule, it can’t be to­tally cured. It can only be con­trolled.

“A typ­i­cal treat­ment plan for a metastatic can­cer pa­tient in­volves find­ing the right drug. We may find one to work for a while and it may stop work­ing. That means we have to go back to our ar­se­nal of op­tions and find some­thing else that works,” said Dr. Chavez-MacGre­gor. “I of­ten tell my pa­tients, I’m like a plumber and I have a belt with a num­ber of tools – those are my ther­a­peu­tic op­tions. I keep us­ing them un­til I find the right tool for the sit­u­a­tion. As physi­cians, we don’t ever want to run out of op­tions. We know there has been a lot of progress in the devel­op­ment of tools, but we want more”.

The FDA re­cently ap­proved three new drugs that Dr. Chavez-MacGre­gor says are a wel­comed ad­di­tion to the fight against ad­vanced stages of breast

® can­cer. The three in­clude: Afin­i­tor (Everolimus), Per­jeta™ (Per­tuzumab) and Kad­cyla™ (TDM1).

The great­est break­through in th­ese new drugs is their abil­ity to “hitch­hike” or “latch onto” the can­cer cells and slow down or even stop their pro­gres­sion.

Everolimus

® Ac­cord­ing to No­var­tis, mak­ers of Afin­i­tor (everolimus), the FDA ap­proval for the drug marks a sig­nif­i­cant mile­stone for women bat­tling ad­vanced

® breast can­cer. The ap­proval of Afin­i­tor : * Rep­re­sents the first ma­jor ad­vance for US pa­tients with ad­vanced HR+ breast can­cer since aro­matase in­hibitors were in­tro­duced more than 15 years ago · In a Phase III trial, Afin­i­tor plus ex­emes­tane more than dou­bled the time women lived be­fore the can­cer wors­ened com­pared to ex­emes­tane alone

® Afin­i­tor (everolimus) is ap­proved for the treat­ment of post­menopausal women with ad­vanced hor­mone re­cep­tor-pos­i­tive, HER2neg­a­tive breast can­cer (ad­vanced HR+ breast can­cer) in com­bi­na­tion with ex­emes­tane af­ter fail­ure of treat­ment with letro­zole or anas­tro­zole .

While en­docrine ther­apy re­mains the cor­ner­stone of treat­ment for th­ese women, most will even­tu­ally de­velop treat­ment re­sis­tance. Ther­a­peu­tic re­sis­tance has been as­so­ci­ated with over­ac­ti­va­tion of the PI3K/AKT/mTOR

® path­way. Afin­i­tor tar­gets the mTOR path­way, which is hy­per­ac­ti­vated in many types of can­cer cells. mTOR is a protein that acts as an im­por­tant reg­u­la­tor of tu­mor cell di­vi­sion, blood ves­sel growth and cell me­tab­o­lism.

TDM1

® “Afin­i­tor is the first and only treat­ment that boosts the ef­fec­tive­ness of en­docrine ther­apy, sig­nif­i­cantly ex­tend­ing the time women with ad­vanced breast can­cer live with­out tu­mor pro­gres­sion,” said Gabriel Hor­to­bagyi, MD, former Chair of Breast Med­i­cal On­col­ogy, Univer­sity of Texas MD An­der­son Can­cer Cen­ter. “This ap­proval re­de­fines the treat­ment and man­age­ment of ad­vanced hor­mone re­cep­tor­pos­i­tive breast can­cer, of­fer­ing a crit­i­cal new op­tion for physi­cians and pa­tients.” The sec­ond new drug ap­proved re­cently by the FDA is Kad­cyla™ (ado-trastuzumab) from Ge­nen­tech. The U.S. Food and Drug Ad­min­is­tra­tion (FDA) ap­proved Kad­cyla™ (ado-trastuzumab em­tan­sine or T-DM1) for the treat­ment of peo­ple with HER2-pos­i­tive metastatic breast can­cer. Kad­cyla™ is the first FDAap­proved An­ti­body Drug Con­ju­gate for treat­ing HER2-pos­i­tive, an ag­gres­sive form of the disease.

In a re­cent study, peo­ple who re­ceived Kad­cyla™ lived a me­dian of 5.8 months longer (over­all sur­vival) than those who re­ceived the com­bi­na­tion of la­p­a­tinib and Xeloda, the stan­dard of care in this set­ting (me­dian over­all sur­vival: 30.9 months vs. 25.1 months). Also, those re­ceiv­ing Kad­cyla™ ex­pe­ri­enced a 32 per­cent re­duc­tion in the risk of dy­ing com­pared to peo­ple who re­ceived other med­i­ca­tions.

Per­tuzumab

The U. S. Food and Drug Ad­min­is­tra­tion ap­proved Per­jeta™ (per­tuzumab), also from Ge­nen­tech, in­jec­tion for use in com­bi­na­tion with trastuzumab and do­c­etaxel for the treat­ment of pa­tients with HER2-pos­i­tive metastatic breast can­cer who have not re­ceived prior an­tiHER2 ther­apy or chemo­ther­apy for metastatic disease. Per­tuzumab tar­gets the cel­lu­lar do­main of HER2.

Per­tuzumab is be­ing stud­ied in early and ad­vanced stages of HER2-pos­i­tive breast can­cer and ad­vanced HER2-pos­i­tive gas­tric can­cer. Per­tuzumab is unique in that it is de­signed specif­i­cally to pre­vent the HER2

re­cep­tor from pair­ing with other HER re­cep­tors, a process be­lieved to play a crit­i­cal role in the growth and for­ma­tion of sev­eral dif­fer­ent can­cer types. By prevent­ing re­cep­tor pair­ing, per­tuzumab is thought to block cell sig­nal­ing, which may in­hibit can­cer cell growth or lead to the death of the can­cer cell. Bind­ing of per­tuzumab to HER2 may also sig­nal the body's im­mune sys­tem to de­stroy the can­cer cells.

The mech­a­nisms of ac­tion of per­tuzumab and Her­ceptin are be­lieved to com­ple­ment each other, as both bind to the HER2 re­cep­tor but on dif­fer­ent re­gions. The goal of com­bin­ing per­tuzumab with Her­ceptin and chemo­ther­apy is to de­ter­mine if the com­bi­na­tion may pro­vide a more com­pre­hen­sive block­ade of HER sig­nal­ing path­ways.

A Mas­sive Chal­lenge

“We have done a lot bet­ter, es­pe­cially with th­ese new ad­vanced ther­a­pies. We cat­e­go­rize ad­vanced breast can­cer into three groups: Horomone re­cep­tor pos­i­tive, HER2 pos­i­tive and Triple Neg­a­tive,” Dr. ChavezMacGre­gor noted. “Of the three, we have made the least progress with Triple Neg­a­tive sub­type be­cause it is the most com­plex. For th­ese tu­mors we don’t have tar­geted ther­a­pies, chemo­ther­apy is our only op­tion and many times the tu­mors be­come re­sis­tant to chemo­ther­apy. We are des­per­ately try­ing to find an­swers. Triple neg­a­tive breast can­cer is our great­est chal­lenge”.

The drugs above rep­re­sent only three ap­provals for vir­tu­ally hun­dreds of other drugs un­der study for the fight against can­cer. The first ques­tion for many, par­tic­u­larly those fight­ing for their lives, is why aren’t we see­ing more med­i­ca­tions be­com­ing avail­able, par­tic­u­larly when time is not on the side of an ad­vanced can­cer pa­tient? Why, with so many in clin­i­cal tri­als, are so few drugs be­ing ap­proved by the FDA?

Dr. Chavez-MacGre­gor ex­plains that while ev­ery­one in­volved in the process – from the pa­tient to the doc­tors to the phar­ma­ceu­ti­cal com­pa­nies to the government – want noth­ing more than more and bet­ter med­i­ca­tions, and while the process seems to be painfully drawn out, it can only be ac­cel­er­ated so much.

“We have to be care­ful,” she pointed out. “We have to be cer­tain the drug is ef­fec­tive and that it has been thor­oughly tested. It could be dis­as­trous to in­tro­duce a drug that hasn’t been prop­erly and thor­oughly tested. If a drug has gone through the proper pro­cesses, and clin­i­cal tri­als, as physi­cians, we can be con­fi­dent in pre­scrib­ing a med­i­ca­tion as part of a treat­ment plan.”

In ad­di­tion to time and money, test­ing a drug re­quires clinic tri­als and pa­tients for th­ese tri­als. Ac­cord­ing to Dr. Chavez-MacGre­gor, clin­i­cal tri­als in­clude thou­sands of pa­tients to ob­tain the nec­es­sary re­sults to safely add a new tool to the bat­tle against breast can­cer.

Ad­e­quate Fund­ing?

Med­i­cal re­search is ex­pen­sive with never a prom­ise of a pos­i­tive out­come. There is a fear from the med­i­cal com­mu­nity that re­cent government spend­ing cuts may af­fect re­search. How­ever, a great deal of drug re­search comes from phar­ma­ceu­ti­cal com­pa­nies look­ing for ef­fec­tive prod­ucts to bring to mar­ket. Other fund­ing comes from non-profit or­ga­ni­za­tions such as the Su­san G, Komen Foun­da­tion, the Breast Can­cer Re­search Foun­da­tion and the Avon Breast Can­cer Foun­da­tion. The process will still re­quire fed­eral government fund­ing through such or­ga­ni­za­tions as the Na­tional Can­cer In­sti­tute. Time will tell if the bud­get cuts will slow down the government’s most im­por­tant role – ap­prov­ing the drugs.

Per­haps the great­est ques­tion on the mind of any ad­vanced stage breast can­cer pa­tient and their doc­tor is: Are we win­ning the war? -Mar­i­ana Chavez-MacGre­gor, MD, MSC

“As can­cer doc­tors, ev­ery day, we get re­minded that we need to do bet­ter. There is no way to give up when you have to tell a 40 year-old woman with two kids at home she has metastatic breast can­cer and that’s it, there is no cure. We can’t do that. It...

“When I was first di­ag­nosed with metastatic breast can­cer, the first thought was my chil­dren. I’m a mother of three daugh­ters, and it was a fear that I have to fight this for my daugh­ters, and this was the first di­ag­no­sis. My daugh­ters im­me­di­ately...

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