Guidelines for Breast Cancer

1991 { var scribd = document.createElement(“script”); scribd.type = “text/javascript”; scribd.async = true; scribd.src = “”; var s = document.getElementsByTagName(“script”)[0]; s.parentNode.insertBefore(scribd, s); })();

Most women with screen-detected breast cancer have not had their life saved by screening

Age-standardised death rates from Breast cance...Image via Wikipedia

 No Comments  No TrackBacks

That’s the conclusion of an article published today in the Archives of Internal Medicine. I’m on the run today, but here’s the abstract

Background Perhaps the most persuasive messages promoting screening mammography come from women who argue that the test “saved my life.” Because other possibilities exist, we sought to determine how often lives were actually saved by mammography screening.

Methods We created a simple method to estimate the probability that a woman with screen-detected breast cancer has had her life saved because of screening. We used DevCan, the National Cancer Institute‘s software for analyzing Surveillance Epidemiology and End Results (SEER) data, to estimate the 10-year risk of diagnosis and the 20-year risk of death–a time horizon long enough to capture the downstream benefits of screening. Using a range of estimates on the ability of screening mammography to reduce breast cancer mortality (relative risk reduction [RRR], 5%-25%), we estimated the risk of dying from breast cancer in the presence and absence of mammography in women of various ages (ages 40, 50, 60, and 70 years).
Results We found that for a 50-year-old woman, the estimated risk of having a screen-detected breast cancer in the next 10 years is 1910 per 100 000. Her observed 20-year risk of breast cancer death is 990 per 100 000. Assuming that mammography has already reduced this risk by 20%, the risk of death in the absence of screening would be 1240 per 100 000, which suggests that the mortality benefit accrued to 250 per 100 000. Thus, the probability that a woman with screen-detected breast cancer avoids a breast cancer death because of mammography is 13% (250/1910). This number falls to 3% if screening mammography reduces breast cancer mortality by 5%. Similar analyses of women of different ages all yield probability estimates below 25%.
Conclusions Most women with screen-detected breast cancer have not had their life saved by screening. They are instead either diagnosed early (with no effect on their mortality) or overdiagnosed.

Breast Cancer Screening

By Graham McMahon

The latest article in our Clinical Practice series reviews current recommendations for breast-cancer screening and thesupporting evidence, including the controversy regarding mammographic screening of women in their 40s.
Worldwide, breast cancer is now the most common cancer diagnosed in women and is the leading cause of deaths from cancer among women, with approximately 1.3 million new cases and 458,000 deaths reported in 2008.OK

Clinical Pearls

 How have the screening recommendations from the U.S. Preventive Services Task Force (USPSTF) changed in recent years?
In contrast to its 2002 guidelines, the more recent recommendations of the USPSTF, published in November 2009, support a reduction in the use of screening mammography. The two most controversial changes were the reclassification of screening for women between the ages of 40 and 49 years from a B recommendation (based on moderately strong evidence) to a C recommendation (“the decision . . . should be an individual one and take into account patient context, including the patient’s values regarding specific benefits and harms”), and the recommendation that the frequency of screening be reduced from every 1 to 2 years to every 2 years.
 What is the consensus recommendation regarding mammographic screening for women between the ages of 50 and 69?
Screening mammography for women 50 to 69 years of age is universally recommended. All but one of the trials that included women in their 60s showed a significant reduction in mortality in the screened group, although this was not true for the subgroup of women in their 50s. Still, a meta-analysis revealed significant reductions in the number of deaths in both these age groups — 14% for women in their 50s and 32% for those in their 60s.

Morning Report Questions

Q: For a 42-year-old woman with no risk factors, what are the benefits and risks of screening mammography?
A: Her chance of having invasive breast cancer over the next 8 years is about 1 in 80, and her chance of dying from it is about 1 in 400. Biennial mammographic screening will detect two out of three cancers in women her age and will reduce her risk of death from breast cancer by 15%. However, there is about a 40% chance that she will be called back for further imaging tests and a 3% chance that she will undergo biopsy, with a benign finding.
Q: What are the benefits of digital mammography?
A: The contrast between breast tumors and surrounding normal parenchyma is greater with digital mammography than with film mammography, particularly when the breast tissue is dense. In one study in which almost 50,000 asymptomatic women 40 years of age or older underwent both digital and film mammography, the two techniques were equivalent overall in sensitivity (70% and 66%, respectively) and specificity (92% for both). However, in women under the age of 50 years, digital mammography was significantly more sensitive than film (78% vs. 51%).
Enhanced by Zemanta

An Avastin Recommendation & Conflicts Of Interest

Earlier this month, the National Comprehensive Cancer Network, a non-profit group of oncologists whose guidance is closely followed by leading treatment centers, voted overwhelmingly in favor of maintaining its recommendation that Avastin should be used to treat breast cancer. The vote came shortly after an FDA panel voted 6-to-0 to revoke the breast cancer indication for Avastin.
The endorsement is important because oncologists will likely continue to use Avastin even if FDA commish Margaret Hamburg rescinds the breast cancer indication. Roche and its Genentech unit had appealed a decision last December by the agency to pull the indication for their best-selling med after new studies showed the med does not prolong overall survival in breast cancer patients or provide a sufficient benefit in slowing disease progression to outweigh significant risks. This prompted the unusual two-day hearing last month (back stories here and here).
However, 10 of the 33 members of the NCCN breast cancer panel members have ties to Roche or Genentech, either as advisory board members, speakers, consultants, expert witnesses or having received clinical research support. These connections are disclosed on the NCCN web site (look here). And 25 members of the panel participated in the recent vote to maintain the recommendation.
Specifically, the NCCN panel voted 24 in favor, 0 against and 1 abstention. The simple math suggests that at least one panel member – and possibly two – with ties to Roche voted to support the metastatic breast cancer recommendation. Perhaps more panel members with connections voted, although there is now way to know ascertain this since the NCCN press release does not specify who participated in the voting.
As we have noted previously, the NCCN endorsement is likely to be a boon for Roche, since treatment for breast cancer has typically generated about $1 billion or more in annual sales. Avastin rings registers – worldwide sales last year totaled about $6.8 billion and rose 9 percent, which meant this one drug accounted for 14 percent of total Roche sales. In other words, much is at stake.
Meanwhile, the stated NCCN policy conflicts of interest requires “disclosure of external relationships and recusal of NCCN Guidelines Panel Members with conflicting interests so that the integrity of the NCCN Guidelines is not compromised or diminished by conflicts or by the perception of conflicts,” according to the NCCN web site.
The policy also states that a panel member with a significant and direct or indirect relationship with “an external entity” that constitutes a conflict shall not participate in NCCN Guidelines Panel discussions, when the panel’s action on the topic under discussion “may advantage or disadvantage an external entity.” An exception is granted when requested by the panel chair “to participate for the purpose of providing or presenting information to the NCCN Guidelines Panel.”
More specifically, certain “direct relationships,” such as a panel member who is a beneficial owner of stock in an “external” entity or a director of such an organization” would be considered to have a de facto conflict. The policy also defines “direct relationships” as anyone “who receives compensation for services including, but not limited to, management or consulting services to the organization” (here is the policy).
So we asked NCCN whether this policy was followed for the recent breast cancer panel, given that the vote tally suggested otherwise. The spokeswoman repeatedly declined to discuss specifics and referred us back to the recent press release which, again, offers no information on the topic. In fact, she refused to answer whether NCCN has a recusal policy, even though this exists on the web site. “I’m only allowed to discuss what is in the press release,” she told us over and over.
We also reached out to the 10 panel members who have ties to Roche and Genentech. One responded. Antonio Wolff wrote us to confirm that “Genentech provides funding to Johns Hopkins University (where I am employed as School of Medicine faculty) to support research costs associated with an ongoing early phase clinical trial, and I am the site PI for that study. As for your specific question regarding my activities within NCCN, I will ask (you) to contact it directly as NCCN requires all panel members to adhere to its confidentiality policy.”
And so, an influential panel with ties to a drugmaker – which has a lot of sales on the line – voted to maintain a key recommendation. In this instance, NCCN panel members fully disclosed their ties to Roche, but is this sufficient? Supposedly, there is a reason NCCN has a disclosure and recusal policy, but in this instance, there would appear to have been a breach. If none occurred, the organization should be willing to discuss specifics and defend its policy. Yet NCCN refused to do so. What do you think?
Source: Pharmalot