MAMMOGRAMS BETTER TO BEGIN AT AGE 40

A new analysis is poised to reignite the debate that has been raging over the value of mammography in women younger than 50 years of age.

There was a furor when the revised US Preventative Service Task Force (USPSTF) recommendations for breast cancer screening were released in November 2009. The most notable changes were to advise against routine screening mammograms for women 40 to 49 years of age, to change the screening interval from 1 to 2 years in women 50 years and older, and to end screening at 74 years.

The updated guidelines became mired in controversy as soon as they were published, as previously reported by Medscape Medical News. A number of organizations, including the American Cancer Society (ACS), the American College of Radiology, and the American College of Obstetricians and Gynecologists, recommended that physicians and patients continue to follow earlier guidelines.

Now, a study published in the February issue of the American Journal of Radiology that analyzed the same data as the USPSTF has come up with very different results.

R. Edward Hendrick, PhD, clinical professor of radiology at the University of Colorado School of Medicine in Denver, and Mark Helvie, MD, director of breast imaging at the University of Michigan Comprehensive Cancer Center in Ann Arbor, found that beginning screening at a younger age and at more frequent intervals can save more lives.

What is most important is to save the most lives," Dr. Hendrick told Medscape Medical News, "not to do the fewest mammograms. If you want to save the most lives, then doing annual mammograms from age 40 to 84 years clearly is superior."

According to the analysis, women who receive annual mammograms starting at age 40 can significantly reduce the risk of dying from breast cancer by 71%. This is in contrast to women who follow the USPSTF recommendations, who had a 23.2% reduction in mortality.

Lower Mortality With Earlier Screening

Dr. Hendrick and Dr. Helvie used 6 model scenarios of screening mammography that were created by the Cancer Intervention and Surveillance Modeling Network, which is the same modeling data used by the USPSTF. They compared mortality reduction for women who followed the 2009 USPSTF recommendations with that for women who followed the ACS recommendations (annual screening beginning at age 40).

"In their summary paper, the USPSTF did not do any averaging over the 6 models," explained Dr. Hendrick. In our analyses, we selected a model that was "somewhere in the middle, but it wasn't an average over the 6."

When the USPSTF looked at any of these modeling data, they chose the point on the graph when it first begins to turn over in terms of mortality reduction per mammogram done. "That was biennial screening beginning at age 50," he said.

In contrast, the authors of new analysis averaged the 6 models and found that for women 40 to 84 years, annual screening conveyed an estimated 39.6% reduction in mortality (range over the 6 models, 29.4% to 54%). This was compared with biennial screening at 50 to 74 years, which showed an estimated mortality reduction of 23.2% (range, 20% to 28%).

They found that approximately 12 lives per 1000 women screened would be saved with annual screening beginning at age 40, whereas with the USPSTF-recommended screening regimen, an estimated 7 lives per 1000 women screened would be saved. Overall, the ACS screening guidelines would result in 5 more lives per 1000 women saved than the USPSTF screening guidelines.

Overemphasis of Harms

The USPSTF also overemphasized the potential harms of screening mammography, explained Dr. Hendrick.

You can't really compare having a call back for additional testing to dying of breast cancer," he said. "They were comparing something with mild implications to something with huge implications. They looked at the potential harms of screening without looking at lives saved from a proper perspective."

The actual number of false-positive tests is also actually quite low, Dr. Hendrick noted. For a woman 40 to 49 years who receives annual screening, a false-positive test will occur once every 10 years on average. She will be recalled for additional imaging once every 12 years and undergo a false-positive biopsy once every 149 years. A missed malignancy will happen once every 1000 years.

In the USPSTF report, the harms of unnecessary recall for additional imaging were emphasized, the authors note. However, "this harm can be mitigated if women elect real-time screening interpretation with same-visit diagnostic imaging offered at many [American] facilities, . . . but this option was not mentioned by the USPSTF report."

May Dissuade Payors

Because the new recommendations were made by a federal panel, they do have an effect on healthcare decisions, Dr. Hendrick said.

In fact, the guidelines could have dissuaded some women from having a screening mammography, and could influence reimbursement from Medicare, Medicaid, and private payors, he added.

The USPSTF recommendations have done potential damage to women's health by failing to seize the singular opportunity to both improve mammography in the United States and to increase screening mammography compliance," say the authors.

Dr. Hendrick reports being a consultant to GE Healthcare and serving on the medical advisory boards of the Koning Corporation and Bracco, both of which develop and manufacture diagnostic imaging systems. Dr. Helvie reports receiving grant support from GE Healthcare.

BONE TURNOVER MARKERS AS PROGNOSTIC FACTORS IN PROSTATE CANCER

Bone Turnover Markers as Predictors of Mortality Risk in Prostate Cancer Patients with Bone Metastases Following Treatment with Zoledronic Acid.

Jung K, Miller K, Wirth M, Albrecht M, Lein M.

Department of Urology, University Hospital Charité, Berlin, Germany; Berlin Institute for Urologic Research, Berlin, Germany.
Abstract

BACKGROUND: Clinical data have limited validity for predicting the survival of prostate cancer (PCa) patients with bone metastases. There is a need to improve the predictive evidence both for clinicians and patients.

OBJECTIVE: To evaluate the predictive ability of serum bone markers for mortality risk in PCa patients with bone metastases.

DESIGN, SETTING, AND PARTICIPANTS: We conducted a survival analysis in relation to bone markers in a subgroup of 52 patients treated with zoledronic acid (4mg every 4 wk for 15 mo) in a prospective, multicentre trial during 2002-2005, about 4 yr after the end of the trial.

MEASUREMENTS: Serum levels of total and bone-specific alkaline phosphatase, amino-terminal procollagen propeptides of type I collagen (PINP), cross-linked N-terminal (NTx) and cross-linked C-terminal telopeptides of type I collagen (ICTP), C-terminal telopeptides of type I collagen, prostate-specific antigen from the last visit of the treatment study, and clinical data were related to the overall survival (OS) status of patients in the follow-up. Univariate and multivariate Cox regression analyses with internal bootstrapping validation and concordance index calculations were performed.

RESULTS AND LIMITATIONS: Out of the 52 patients followed, 34 died within a median follow-up of 13.8 mo, and 18 patients were alive at a median follow-up of 43.8 mo. The patients who died within the follow-up period had significantly higher concentrations of ICTP, NTx, and PINP than the surviving patients. Cox regression models with clinical data and bone markers showed that ICTP and PINP were most predictive for mortality risk in addition to the occurrence of skeletal-related complications and the continuation of treatment with zoledronic acid. Internal validation confirmed the reliability of the results, although the sample size was small.

LUNG CANCER STAGING

FINGER LENGTH AND PROSTATE CANCER RISK

Men whose index finger is longer than their ring finger are at a lower risk of prostate cancer than those with a finger pattern the other way round, according to a new study in the British Journal of Cancer.

The relative length of the first and third fingers is set before birth, and it is thought to relate to the levels of sex hormones the baby is exposed to in the womb. Babies exposed to less of the male sex hormone testosterone are more likely to have longer index fingers.

Finger Length and Prostate Cancer

Over a 15-year period, researchers from The University of Warwick and The Institute of Cancer Research (ICR) collected data on finger length in 1,524 patients with prostate cancer as well as 3,044 healthy people. Men were shown pictures of hands with different finger lengths and asked to identify the one most like their own right hand.

The most common finger length pattern, seen in more than half the men in the study, was a shorter index than ring finger. Men whose index and ring fingers were the same length (about 19%) had a similar prostate cancer risk to those with a shorter index than ring finger. However, men whose index fingers were longer than their ring finger were 33% less likely to have prostate cancer.

Risk reduction was even greater in men aged under 60, say the researchers, who found that this younger group were 87% less likely to be in the prostate cancer group.

Testosterone Exposure

The researchers believe that being exposed to less testosterone before birth helps protect against prostate cancer later in life. The phenomenon is thought to occur because the genes HOXA and HOXD control both finger length and development of sex organs.

“Our results show that relative finger length could be used as a simple test for prostate cancer risk, particularly in men aged under 60,” says joint senior author Professor Ros Eeles from the ICR and The Royal Marsden NHS Foundation Trust. “This exciting finding means that finger pattern could potentially be used to select at-risk men for ongoing screening, perhaps in combination with other factors such as family history or genetic testing.”

The study was funded by Prostate Cancer Research Foundation and Cancer Research UK.

Diagnosing Prostate Cancer

Helen Rippon, head of research at The Prostate Cancer Charity in the U.K., says in an emailed statement: “Diagnosis of prostate cancer is not a simple affair and the best blood test we have, known as a PSA test, tells us only that something might be wrong with the prostate, not whether it is cancerous or not. Anything that adds to our knowledge about whether a man is likely to develop prostate cancer or not is to be welcomed, especially when it is something as easy as looking at the length of his fingers.

“This research also adds to the growing body of evidence that the balance of hormones we are exposed to before birth influences our health for the rest of our lives.”

Rippon says men who check their hands and find they have a shorter index finger should not be unduly concerned. “They share this trait with more than half of all men and it does not mean they will definitely develop prostate cancer in later life,” she says.

ESTROGEN MODIFIES LUNG CANCER OUTCOME

More evidence that estrogen modifies the outcome of lung cancer comes from a huge study of women with breast cancer, about half of whom were taking antiestrogens such as tamoxifen.
Among the women who subsequently developed lung cancer, the use of antiestrogens was associated with a significantly reduced risk for death from lung cancer, compared with the general population.
The finding comes from a study published online January 24 in Cancer.
"Our results support the hypothesis that there is a hormonal influence on lung cancer, which has been suggested by findings such as the presence of estrogen and progesterone receptors in a substantial proportion of lung cancers," senior author Elisabetta Rapiti, MD, from the Geneva Cancer Registry, said in a statement.
"If prospective studies confirm our results and find that antiestrogen agents improve lung cancer outcomes, this could have substantial implications for clinical practice," she added.
Approached by Medscape Medical News for independent comment, Howard West, MD, from the Swedish Cancer Institute in Seattle, Washington, said: "These results are very provocative, especially since they are compatible with the findings from the Women's Health Initiative [WHI], which demonstrated a higher mortality rate from lung cancer in women who received estrogen and progestins, compared with the placebo arm."
"I completely agree that these results warrant prospective testing of antiestrogens," Dr. West continued. "Until we have results from such trials, I would be inclined to discuss these results with women who are taking hormone replacement therapy, as I already do, which may lead to their stopping hormone replacement therapy after considering the balance of benefit vs risk. I wouldn't, however, go so far as to say that these results justify giving antiestrogen therapy as a treatment for lung cancer."
Study Prompted by WHI Findings
The current study was, in fact, prompted by those findings on lung cancer from the WHI study, the authors explain.
When that finding was published, the WHI researchers noted that "treatment with estrogen plus progestin in postmenopausal women did not increase incidence of lung cancer, [but] it increased the number of deaths from lung cancer, in particular deaths from nonsmall-cell lung cancer."
Dr. Rapiti and colleagues, including first author Christine Bouchardy, MD, hypothesized that if it is true that hormone therapy increases the risk for lung cancer death, then the use of antiestrogens should be associated with a decreased risk for lung cancer death.
This was, indeed, what they found.
The team analyzed data from 6655 women with breast cancer from the Geneva Cancer Registry, nearly half of whom (46%) had taken antiestrogens.
Over a median follow-up of 7.3 years, the researchers found that 40 of these women developed lung cancer. The incidence of lung cancer was similar in the group taking and the group not taking antiestrogens (P = .39).
The team then compared outcomes for this small group of women with population results from standardized mortality ratios.
They found that the incidence of lung cancer was similar among women who had and had not taken antiestrogens and the general population.
However, the risk for death from lung cancer was significantly lower in women who had taken the drugs than in those who had not, and than in the general population. Specifically, there were 87% fewer cases of death from lung cancer in the antiestrogen group than in the general population.
Lung cancer mortality rates were 9.2 per 100,000 for women taking antiestrogens and 45.0 per 100,000 for women not taking these drugs (P = .026).
The finding is unlikely to be due to differences in smoking, the authors note, because patterns of tobacco exposure were similar in the 2 groups. However, they also note that they obtained this information for only about half of the entire cohort.
New Evidence for the Role of Estrogen
The team concludes: "In analyses comparing tumor registry to population results from standardized mortality ratios, we found that antiestrogen treatment for breast cancer was associated with a reduced risk of death from lung cancer, providing new evidence on the role of estrogen in lung cancer progression."
"From a biological perspective, the observation that estrogen intake is associated with increased lung cancer mortality, and that antiestrogen treatment is associated with a decreased lung cancer mortality, as demonstrated in this study, strongly suggests that estrogens are involved in lung cancer progression," they add.
When approached for independent comment by Medscape Medical News, Dr. West noted that the finding showed a significant reduction in the rate of lung cancer mortality among women who were taking antiestrogens, compared with age-adjusted mortality rates in the general population.
"In fact, the rate was only 13% of the calculated result that would be expected, a statistically significant difference," he said.
"However, these results are predicated on a very small number of patients, compared with a prediction based on a model," Dr. West pointed out.