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A step forward in personalized medicine for treatment-refractory metastatic breast cancer 

MD-FM Thursday February 13, 2014 

 

Sarah:

MD-FM, Medical News from around the world with Peter Goodwin.

 

BREAST CANCER: first large-scale genome-wide study identifies new targetable mutations for investigational drugs 

 

PETER:

Hello, and Sarah Maxwell is here with me.

For patients with breast cancer that’s refractory to standard treatments, there’s hope coming from the first large-scale trial looking at a new approach to personalized medicine. The entire genome was scanned in more than 400 women with metastatic breast cancer to help identify genomic alterations that can be targeted with new agents currently under investigation…

 

SARAH:

Yes, nearly half of the women enrolled in the study were found to have at least one targetable genomic alteration. 28% of those, were then deemed eligible to be enrolled in phase I and II clinical trials testing new therapeutic options. The investigators hope that in the future, more women could be matched with treatments by using this ‘whole-genome’ approach. Professor Charles Swanton wrote an editorial on the study in the New England Journal of Medicine:

 

SWANTON:

Because breast cancer is a myriad of different diseases we need a myriad of different clinical trials available to enable patients to access them once we have results in their tumour genomic data.

 

SARAH:

That was Charles Swanton from the Cancer Research UK London Research Institute. Of the 55 patients who actually got a new treatment in the study, 30% responded.  That’s a small group, but nonetheless it’s promising for patients who currently have no options. Lead study author, Fabrice André:

 

ANDRE:

This genomic analysis has been done in just a little bit more than one year, so in fact it’s a scale up that opens the door of personalized medicine. Now that we have shown that it is feasible, we need to know whether this approach is going to improve the outcome of the patients, and this is the topic of three randomized trials that are now being led in France.

 

SARAH:

That was Professor Fabrice André, from Institut Gustave Roussy in Villejuif, France.

 

 

SEGMENT 2: Prophylactic double mastectomy: better survival than single mastectomy for women with BRCA breast cancer gene mutation


PETER:

Women who have a mutated BRCA breast cancer gene, were significantly less likely to die if they have a double mastectomy rather than only one breast removed. That’s the finding of a study looking at 390 patients — published in the British Medical Journal — that showed over 20 more lives could be saved per 100 women. But the authors say because of the small numbers in their study further research is still needed to confirm these findings.

 

SEGMENT 3: Two doses of the human papillomavirus vaccine still reduced the risk of genital warts 

 

PETER:

Two doses of the human papillomavirus vaccine, instead of the current standard three, still resulted in a reduced risk of genital warts. That was the finding of a population-based study reported in JAMA…

 

SARAH:

That’s right, although three shots of HPV vaccine had the maximum reduction in risk, just two shots was still associated with a substantially decreased risk. In a nutshell: they found you get 384 fewer cases of genital warts per 100 000 person-years if you have even a single dose. Slightly more cases prevented — 400 — with two shots and a little more still — 459 cases per 100 000 person years if you have three shots.

 

PETER:

So one shot is highly protective; two slightly more so, and three slightly more still! And as these vaccines are quite expensive for some countries, you can understand why some young women don’t even show up for three rounds of HPV vaccination!

 

SARAH:

Yes, and it’s a good thing that one is still quite good! Actually in some countries, like Chile and British Columbia, two doses is already within the standard recommended vaccination program. However, the authors cautioned that, more research is needed before fewer doses can be widely recommended. The main reason women get vaccinated against HPV — of course —  is to prevent cervical cancer: and there just aren’t enough data available on that yet. Senior author Dr. Arnheim-Dahlström:

ARNHEIM-DAHLSTRÖM:

I think it’s important to keep in mind here that we studied condylomas, which is not the same thing as cervical cancer. Cervical cancer takes decades to develop so we really don’t know what the results would look like… And also the clinical trials so far, they have not really studied disease outcome by dose level yet --they are looking at antibody response. What they can see so far is that the younger you are when you get the vaccine, you have a better immune response. So maybe then vaccinating when you are a bit younger would also mean that you have a better and more long-lasting immune response. Another aspect that we could not look at in our study is herd immunity… So there are different things to consider here, not only 3 vs. 2 doses.

 

SARAH:

That was Lisen Arnheim-Dahlström, from the Karolinska Institutet in Stockholm.

 

SEGMENT 4: Sentinel-node biopsy beneficial for all patients with intermediate-thickness primary melanoma

 

PETER:

New findings strongly support and reinforce guidelines made by the American Society of Clinical Oncology and the Society of Surgical Oncology recommending sentinel-node biopsy for all patients with intermediate-thickness primary melanoma. So, that’s greater than 1.2mm thickness but less than 3.5...

 

SARAH:

That’s right, biopsy-based staging of intermediate-thickness or thick primary melanomas helped identify patients with nodal metastases who might benefit from immediate complete lymphadenectomy compared with watchful waiting. That’s according to 10-year results from the Multicenter Selective Lymphadenectomy Trial; and study co-author Alistair Cochrane gave MDFM the details:

 

COCHRAN:

The patients treated by the sentinel node biopsy approach have an extension of disease-free survival of 3.2 times, distant disease free survival is extended by 2.1 times, and melanoma specific-survival is doubled. So I think the summary would be that biopsy-based staging of intermediate or thick primary melanoma provides accurate and important prognostic information and identifies patients with early nodal metastasis who might benefit from immediate complete lymphatectomy.

 

SARAH:

That was Alistair Cochran, from the University of California in Los Angeles. He said that while survival benefits were particularly clear in patients with intermediate-size tumours, the melanoma-specific and distant-disease free survival benefits of sentinel node biopsy, were less compelling were less compelling in patients with thick melanomas and further studies are needed in these sub-populations.

 

SEGMENT 5: Young stroke victims should be screened for drug use at hospital admission

 

PETER:

Should young stroke patients be screened systematically for drug use at the time of hospital admission? That’s what researchers suggested at the International Stroke Conference held this week in San Diego:

 

SARAH:

Yes, the risk of ischemic stroke increased six to seven times within the 24 hours following cocaine use — regardless of how it was taken. That was in a study looking at over 1100 people aged 15 to 49 who had a stroke, compared to the same number of controls. In these young adults, cocaine use was a much greater risk factor than other known predictors, such as hypertension, diabetes and smoking. Dr Yu-Ching Cheng presented the results at the meeting:

 

CHENG:

Cocaine can cause the constriction of blood vessels and it can also increase blood pressure, the heart rate and decrease the oxygen supply to the brain… So these physiological effects may boost the risk of stroke.

 

SARAH:

That was Dr Yu-Ching Cheng, from the Veterans Affairs Medical Centre in Baltimore. In previous studies, cocaine use had also been associated with haemorrhagic stroke and myocardial infarctions; and experts suggest patients should be screened when they enter the Emergency Room:

 

NAVAL:

Patients who come in with an ischemic stroke, a haemorrhagic stroke –with any kind of stroke, even maybe with altered mental status, should routinely get drug screening. You know this is not something that happens in the country, it doesn’t happen routinely and it absolutely should because it does potentially have an impact on outcomes and it does potentially have an impact on how we treat these patients.

 

SARAH:

That was Dr Neeraj Naval, from Johns Hopkins Hospital, in Baltimore, who did not participate in the study.



IN BRIEF 1: Preterm birth associated with higher incidence of elevated insulin levels during early childhood

 

PETER:

Finally in brief: more data on the disadvantages of preterm birth are emerging. Apparently, children born prematurely were more likely to have elevated insulin levels during early childhood than those born at term. That’s according to research looking at nearly 1,400 children — published in JAMA — that suggests preterm birth may be a risk factor for the future development of insulin resistance and type-2 diabetes. And...

 

 IN BRIEF 2: New drug combination more effective than standard treatment to cure trichuriasis

 

PETER:

For children infected by the intestinal parasitic nematode known as the whipworm, combining albendazole with oxantel pamoate had higher trichuriasis cure rates and higher rates of egg-reduction than standard treatments, which consist of albendazole or mebendazole given alone. These are the findings of a double blind trial — published in the New England Journal of Medicine — that shows this new combination however, had little efficacy against parasitic infections caused by the hookworm or the giant roundworm Ascaris lumbricoide.


PETER:

That's all from MDFM for now. Sarah Maxwell and I will be back with more next week, so until then from me, Peter Goodwin, goodbye!

 

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