Men in their 60s with prostate cancer are twice as likely as their cancer-free peers to have had androgenic alopecia (or male pattern baldness) begin in their 20s, French investigators report in the Annals of Oncology.
In a retrospective case–control study, men in their late 60s with prostate cancer had an odds ratio of 2.01 for androgenic alopecia at age 20 (95% confidence interval, 1.07 to 3.70; P = .0285), compared with age-matched controls.
However, although early hair loss might be a risk marker for prostate cancer later in life, there was no association between premature balding and advanced tumor stage, high Gleason score (7 or greater), or high prostate-specific antigen (PSA) level (>20 ng/mL), the researchers report.
Receding hairlines did not correlate with an early prostate cancer diagnosis, and the pattern of hair loss was not predictive of tumor aggressiveness, the authors found.
Nonetheless, alopecia's early assault on male vanity could help identify young men at risk for prostate cancer, the authors contend.
"An improved knowledge of risk factors, especially those that are easily identifiable in the patient, may allow us to target a population at high risk of developing prostate cancer and that may benefit from screening or chemoprevention," they write.
Lead researcher Michael Yassa, MD, currently assistant professor of medicine at the University of Montreal in Quebec, Canada, told Medscape Medical News that the findings suggest an avenue of investigation into the origins of prostate cancer.
"I think that further research should [focus] on finding the exact link between hair loss, androgens, and prostate cancer — what exactly links those 3 together. Maybe that will give us more information about what to do with these people," he said.
A better understanding of that interplay could answer questions about whether men with a history of early balding could benefit from earlier screening or chemoprophylaxis with a 5-alpha reductase inhibitor (finasteride, dutasteride) or other agents, he and his coauthors suggest.
But a prostate cancer expert who was not involved in the study told Medscape Medical News that an early risk marker, even if it is validated in further studies, might do more harm than good.
"Most of the diagnoses that are made in younger people are not important to make; they alter a person's life and I really don't want people thinking about the specter of prostate cancer when they're very young," said Donald S. Kaufman, MD, director of the Claire and John Bertucci Center for Genitourinary Cancers at Massachusetts General Hospital in Boston.
In addition, the authors' assertion that prostate cancer could be prevented with finasteride or dutasteride is controversial, Dr. Kaufman said.
"I don't think that's something we all would agree with," he said.
Pattern Recall
The investigators recruited 388 prostate cancer patients from databases from radiation oncology follow-up clinics in Paris and Toulouse, France, and 281 age-matched controls with no history of prostate cancer or hormonal disorders from the same hospital databases.
The participants (mean age, 67.2 years for cases; 66.4 years for controls) were mailed a questionnaire asking about their prostate cancer history, paternal prostate cancer, and balding history. They were also asked to recall and score their balding patterns at ages 20, 30, and 40, using a modified Hamilton-Norwood scale.
In addition, physicians of the respondents were sent a questionnaire confirming or ruling out prostate cancer history. Physicians of cases were asked the patient's age at diagnosis, disease stage at presentation (including TNM stage, Gleason score, and initial PSA level), primary therapy, treatment failures, time between treatment and failure, and their most recent medical impression of the disease (remission, failure, or metastasis).
The authors found that any balding at 20 years, but not at 30 or 40 years, was associated with an increased prostate cancer incidence later. There were no significant associations between the pattern of hair loss (frontal, vertex, or both) and the later development of prostate cancer, and early-onset alopecia was not associated with early-onset prostate cancer. There was also no association between early-onset disease and more aggressive tumors, defined as stage T3–T4, a Gleason score of 7 or higher, or a PSA greater than 20 ng/mL.
The study's funding source was not disclosed. Dr. Yassa, his coauthors, and Dr. Kaufman have disclosed no relevant financial relationships.
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HEDGEHOG INHIBITORS FOR BASAL CELL CARCINOMA
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(New Orleans, Louisiana) — The investigational hedgehog pathway inhibitor GDC-0449 (Genentech) has shown "dramatic" efficacy in reducing the number of new and existing basal cell skin cancers in patients with basal cell nevus syndrome (BCNS), according to research presented here at a late-breaking study session at the American Academy of Dermatology 69th Annual Meeting.
"Currently, surgery is the standard treatment for basal cell carcinoma [BCC]. However, surgery is not an option for patients with really bad BCCs, locally aggressive or metastatic disease, and certainly not for patients who suffer from this genetic disorder of basal cell nevus syndrome," said Jean Y. Tang, MD, from Stanford University in Palo Alto, California. "There is no treatment to prevent these tumors and these patients [undergo] hundreds of surgeries in their lifetime."
Patients with BCNS, also known as Gorlin syndrome, and BCC tumors have mutations in components of the hedgehog signaling pathway that keep it constantly turned on and lead to tumor cell growth and proliferation.
"Molecularly targeted therapies focus on turning this pathway off, and one way to do that is to antagonize the smoothened receptor, which would inactivate the pathway and stop BCC growth," Dr. Tang explained. "GDC-0449 is a small molecule that does just this. It targets the hedgehog pathway by binding to the smoothened receptor. Therefore, we hypothesized that it would stop BCC development in patients with BCNS."
Accordingly, Dr. Tang and her team initiated a phase 2 randomized double-blind placebo-controlled trial in which they enrolled 41 patients from 3 centers and assigned them in a 2:1 ratio to receive oral GDC-0449 150 mg or placebo once daily for 18 months.
The average age of the patients was 54 to 60 years, and they were balanced in terms of sex and weight. At baseline, both groups had 23 or 24 BCCs; they were followed for an average of 8 months.
The researchers found that subjects who were randomized to GDC-0449 had very few BCCs develop over time — 0.07 BCCs per month — compared with 1.74 BCCs per month for patients on placebo (P < .0001). GDC-0449 also significantly reduced the size of existing BCCs (P = .006).
Dr. Tang reported that some patients achieved a near-complete remission and that no resistance to the drug developed.
Palmar pits, a common feature of BCNS, disappeared among patients on the active drug. "Our patients are just struck by this. They've lived with this all their lives and now they can comfortably shake the hands of strangers," she noted.
Because of the big difference in the results, the data safety and monitoring board voted to end the placebo group. The investigators are currently converting participants in the placebo group to the active drug and testing different regimens.
"We're really excited as dermatologists because we're sick of just chopping up these poor patients' skin and we're excited to offer something better," she said.
In an interview with Medscape Medical News, Dr. Tang admitted she is elated with these results. "It is fantastic to us. It feels like this drug could really change the treatment and management of BCCs in these unfortunate patients. For the first time ever, there's something that works besides surgery."
Adverse Effects a Problem for Some
The adverse effects — most notably loss of taste, muscle cramps, and hair thinning — caused 20% of patients to stop treatment.
"These side effects may limit the drug's usefulness. I would tell a patient with this syndrome that if they have a big burden of disease — we're talking 50 or more BCCs — the side-effect profile is worth it, but if they have less than 10 or 20, I'm not sure the side effects are worth it," she said. "But these kinds of discussions need to be made on an individual patient-by-patient basis."
The researchers want to determine whether GDC-0449 can be given intermittently.
"I think because of the side-effect profile, most patients probably won't tolerate taking it every single day for the rest of their lives. Most likely this medication would be given in low doses, or perhaps patients can be on it for 6 or 12 months every few years just to clean up and reduce the burden of BCC tumors on their skin," she said.
The response from the patients has been extremely positive, Dr. Tang said.
"Basically, all of the BCNS patients are connected to each other on Facebook now. One of the first came back to us in tears and told us 'Doctor, this is the first month I've never had a biopsy in 10 years'. The patients are incredibly grateful for this treatment," she said.
The adverse effects are impossible to hide; as a result, patient advocacy groups have been questioning the ethics of having a placebo group, Dr. Tang added.
"Going forward, we won't have one anymore, but it was important to establish our statistical end points," she said.
"This is the first ever molecularly targeted drug against the hedgehog pathway for basal cells, and it basically opens up a new era for treatments of basal cell cancers," Dr. Tang said. "There are a lot of other tumors that are hedgehog-driven, and we hope that whatever we learn in this trial can help other patients with hedgehog-driven tumors."
Richard L. Gallo, MD, PhD, told Medscape Medical News that he found the results of this study "exciting."
"This is a great example of the benefit of understanding the molecular pharmacology of some of these drugs and the pathophysiology behind the origin of these diseases, so the results are very encouraging," he said after the presentation.
"It appears that the side-effect profile so far is very tolerable in this patient population," noted Dr. Gallo, who moderated the late-breaking abstract session. "Clearly, the comments from the patient advocates support what the investigators are saying. I think there will be only good things to say about this in the future."
This study was supported by Genentech. Dr. Tang has disclosed no relevant financial relationships. Dr. Gallo reports financial relationships with Allergan, Ceregenex, Galderma, Inimex, Intendis, Johnson and Johnson, Novartis, and Skin Epibiotics.
"Currently, surgery is the standard treatment for basal cell carcinoma [BCC]. However, surgery is not an option for patients with really bad BCCs, locally aggressive or metastatic disease, and certainly not for patients who suffer from this genetic disorder of basal cell nevus syndrome," said Jean Y. Tang, MD, from Stanford University in Palo Alto, California. "There is no treatment to prevent these tumors and these patients [undergo] hundreds of surgeries in their lifetime."
Patients with BCNS, also known as Gorlin syndrome, and BCC tumors have mutations in components of the hedgehog signaling pathway that keep it constantly turned on and lead to tumor cell growth and proliferation.
"Molecularly targeted therapies focus on turning this pathway off, and one way to do that is to antagonize the smoothened receptor, which would inactivate the pathway and stop BCC growth," Dr. Tang explained. "GDC-0449 is a small molecule that does just this. It targets the hedgehog pathway by binding to the smoothened receptor. Therefore, we hypothesized that it would stop BCC development in patients with BCNS."
Accordingly, Dr. Tang and her team initiated a phase 2 randomized double-blind placebo-controlled trial in which they enrolled 41 patients from 3 centers and assigned them in a 2:1 ratio to receive oral GDC-0449 150 mg or placebo once daily for 18 months.
The average age of the patients was 54 to 60 years, and they were balanced in terms of sex and weight. At baseline, both groups had 23 or 24 BCCs; they were followed for an average of 8 months.
The researchers found that subjects who were randomized to GDC-0449 had very few BCCs develop over time — 0.07 BCCs per month — compared with 1.74 BCCs per month for patients on placebo (P < .0001). GDC-0449 also significantly reduced the size of existing BCCs (P = .006).
Dr. Tang reported that some patients achieved a near-complete remission and that no resistance to the drug developed.
Palmar pits, a common feature of BCNS, disappeared among patients on the active drug. "Our patients are just struck by this. They've lived with this all their lives and now they can comfortably shake the hands of strangers," she noted.
Because of the big difference in the results, the data safety and monitoring board voted to end the placebo group. The investigators are currently converting participants in the placebo group to the active drug and testing different regimens.
"We're really excited as dermatologists because we're sick of just chopping up these poor patients' skin and we're excited to offer something better," she said.
In an interview with Medscape Medical News, Dr. Tang admitted she is elated with these results. "It is fantastic to us. It feels like this drug could really change the treatment and management of BCCs in these unfortunate patients. For the first time ever, there's something that works besides surgery."
Adverse Effects a Problem for Some
The adverse effects — most notably loss of taste, muscle cramps, and hair thinning — caused 20% of patients to stop treatment.
"These side effects may limit the drug's usefulness. I would tell a patient with this syndrome that if they have a big burden of disease — we're talking 50 or more BCCs — the side-effect profile is worth it, but if they have less than 10 or 20, I'm not sure the side effects are worth it," she said. "But these kinds of discussions need to be made on an individual patient-by-patient basis."
The researchers want to determine whether GDC-0449 can be given intermittently.
"I think because of the side-effect profile, most patients probably won't tolerate taking it every single day for the rest of their lives. Most likely this medication would be given in low doses, or perhaps patients can be on it for 6 or 12 months every few years just to clean up and reduce the burden of BCC tumors on their skin," she said.
The response from the patients has been extremely positive, Dr. Tang said.
"Basically, all of the BCNS patients are connected to each other on Facebook now. One of the first came back to us in tears and told us 'Doctor, this is the first month I've never had a biopsy in 10 years'. The patients are incredibly grateful for this treatment," she said.
The adverse effects are impossible to hide; as a result, patient advocacy groups have been questioning the ethics of having a placebo group, Dr. Tang added.
"Going forward, we won't have one anymore, but it was important to establish our statistical end points," she said.
"This is the first ever molecularly targeted drug against the hedgehog pathway for basal cells, and it basically opens up a new era for treatments of basal cell cancers," Dr. Tang said. "There are a lot of other tumors that are hedgehog-driven, and we hope that whatever we learn in this trial can help other patients with hedgehog-driven tumors."
Richard L. Gallo, MD, PhD, told Medscape Medical News that he found the results of this study "exciting."
"This is a great example of the benefit of understanding the molecular pharmacology of some of these drugs and the pathophysiology behind the origin of these diseases, so the results are very encouraging," he said after the presentation.
"It appears that the side-effect profile so far is very tolerable in this patient population," noted Dr. Gallo, who moderated the late-breaking abstract session. "Clearly, the comments from the patient advocates support what the investigators are saying. I think there will be only good things to say about this in the future."
This study was supported by Genentech. Dr. Tang has disclosed no relevant financial relationships. Dr. Gallo reports financial relationships with Allergan, Ceregenex, Galderma, Inimex, Intendis, Johnson and Johnson, Novartis, and Skin Epibiotics.
INTENSIVE CHEMOTHERAPY INCREASES SURVIVAL OF OLDER TEENAGERS WITH ALL
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Historically, older teenagers (those aged 15 - 18 years) with acute lymphoblastic leukemia (ALL) have had a much worse prognosis than younger patients.
Now, however, physicians at St. Jude Children's Research Hospital in Memphis, Tennessee, report that most older adolescents with ALL can be cured with intensive chemotherapy that takes into account their individual risk profile — without stem cell transplantation and without radiation to the brain.
This report was published online December 20 in the Journal of Clinical Oncology.
"The contemporary clinical trials for ALL show 5-year survival rates of 83% to 94% in children and much lower rates — anywhere from 27% to 59% — for older teens and adults," said lead author Ching-Hon Pui, MD, chairman of oncology at St. Jude.
"But with our latest protocol, which uses more effective risk-adjusted chemotherapy and sophisticated patient monitoring, we were able to push the cure rates for older teens to nearly 88%, essentially closing the survival gap between older and younger patients," he told Medscape Medical News.
Older teenagers are difficult to cure because they tend to have more high-risk leukemia, suffer more toxic adverse effects from their treatment, and are less likely to be compliant with their therapy.
"Teens are well known to be less compliant. For example, if they're invited to a party, they won't take their medicine because they don't want to be sick. Or they forget, because they have to take pills 3 times a day," Dr. Pui said. "Teens with chronic illness are notorious for compliance issues. With younger children, it's easier. They are supervised by their parents, who make sure they take their medicine as prescribed."
Study Details
In this report, Dr. Pui and his team compared the long-term survival of 963 pediatric patients, including 89 older adolescents, treated between 1991 and 2007 who were enrolled in 4 consecutive Total Therapy studies — studies XIIA, XIIB, XIV, and XV — that used protocols developed at St. Jude.
In the first 3 studies, treatment selection was based on presenting clinical features and leukemic cell genetics. In study XV, measuring the level of minimal residual disease (MRD) either by flow cytometry or polymerase chain reaction, was used to monitor the patient's response to and compliance with treatment, which featured intensive methotrexate, glucocorticoid, vincristine, and asparaginase, as well as early triple intrathecal therapy for higher-risk ALL.
In the Total XV study, any patient with 1% or more bone marrow MRD on day 19 of remission induction, or 0.1% to 0.99% MRD after completion of induction therapy, was considered to have standard-risk ALL. Patients who were unable to achieve morphologic remission or who had presence of MRD 1% or greater after completion of induction therapy and persistence of MRD 0.1% or greater beyond week 7 of continuation treatment were deemed to have high-risk ALL and became candidates for allogeneic stem cell transplantation.
The Total XV regimen also replaced radiation of the brain with intrathecal chemotherapy. Patients with low-risk disease received 13 to 18 intrathecal treatments, and patients with standard-risk disease received 16 to 25 intrathecal treatments. Prophylactic cranial irradiation was not used, as per the protocol of Total XV.
Survival Rate Increased Significantly With XV Protocol
In the earlier studies, the 5-year event-free survival rate and the 5-year overall survival rate for the 44 older adolescents were both 59.1% (95% confidence interval [CI], 43% - 72%). This was "strikingly" inferior to the event-free survival rate of 82.6% (95% CI, 78.5% - 86%; P < .001) and the overall survival rate of 88.3% (95% CI, 84.7% - 91.1%) achieved in the 403 younger patients, the investigators reported.
In contrast, in study XV, the 5-year event-free survival rates were 86.4% ± 5.2% (standard error) for the 45 older adolescents and 87.4% ± 1.7% for the 453 younger patients. The 5-year overall survival rates were 87.9% ± 5.1% for the older teenagers and 94.1% ± 1.2% for the younger patients.
In addition, patients treated in study XV were less likely to suffer serious late treatment effects, including second cancers and infertility. "Our patients had a good quality of life. We have followed them for over 10 years, and of the 500 patients, only one developed a secondary cancer," Dr. Pui noted. "This is the lowest for any protocol."
Dr. Pui also said that his study highlights the fact that good results in pediatric ALL can be achieved without the use of radiation. It also underlines the importance of personalizing therapy and being aware of compliance.
"We do not give everyone the same dose. Instead, we base the dose on individual pharmacokinetics and pharmacodynamics. We pay close attention to compliance. We monitor patients regularly, and we can tell who is not taking their oral medications. We counsel these patients until they become compliant, and we keep checking to make sure they stay compliant. This is very important, especially for the older teens," Dr. Pui said.
The study also reinforces the growing body of evidence that suggests older teenagers and even young adults with ALL do better on pediatric — as opposed to adult — protocols.
"Pediatric ALL specialists who treat adolescents love to see this kind of data get published," Susan Rheingold, MD, assistant professor of medicine at Children's Hospital of Philadelphia in Pennsylvania, told Medscape Medical News.
Studies have been showing since the early 2000s that older teenagers and young adults do better on pediatric protocols than adult protocols, she said. "In general, the pediatric protocols had a 65% 5-year cure rate, and the adult protocols had a 45% cure rate. When those results began to come out, pediatric oncologists started to say, 'We need to be treating these older adolescents. We need to be treating them like 10-year-olds, and not like 70-year-olds, so we can improve their cure rate. And when it's a 20% higher cure rate — that's significant," she said.
Dr. Rheingold noted that the protocols of the Children's Oncology Group are open to patients up to the age of 30 years.
"You don't stop being a child automatically at the age of 18. Our university hospital [University of Pennsylvania Medical Center] is hearing the message that pediatric oncologists are curing these young adult patients at higher rates with chemo and without transplants, and are sending us patients who are in their 20s," she said.
"The emergency rooms between the adult hospital and the pediatric hospital are probably no further than 100 feet apart. A 21-year-old can walk into either emergency room with a new diagnosis of leukemia, and you would hate to think that what door they chose to walk into could change their cure rate by 10% or 20%."
This research was supported in part by the National Institutes of Health, the American Cancer Society, and the American Lebanese Syrian Associated Charities. Dr. Pui and Dr. Rheingold have disclosed no relevant financial relationships.
Now, however, physicians at St. Jude Children's Research Hospital in Memphis, Tennessee, report that most older adolescents with ALL can be cured with intensive chemotherapy that takes into account their individual risk profile — without stem cell transplantation and without radiation to the brain.
This report was published online December 20 in the Journal of Clinical Oncology.
"The contemporary clinical trials for ALL show 5-year survival rates of 83% to 94% in children and much lower rates — anywhere from 27% to 59% — for older teens and adults," said lead author Ching-Hon Pui, MD, chairman of oncology at St. Jude.
"But with our latest protocol, which uses more effective risk-adjusted chemotherapy and sophisticated patient monitoring, we were able to push the cure rates for older teens to nearly 88%, essentially closing the survival gap between older and younger patients," he told Medscape Medical News.
Older teenagers are difficult to cure because they tend to have more high-risk leukemia, suffer more toxic adverse effects from their treatment, and are less likely to be compliant with their therapy.
"Teens are well known to be less compliant. For example, if they're invited to a party, they won't take their medicine because they don't want to be sick. Or they forget, because they have to take pills 3 times a day," Dr. Pui said. "Teens with chronic illness are notorious for compliance issues. With younger children, it's easier. They are supervised by their parents, who make sure they take their medicine as prescribed."
Study Details
In this report, Dr. Pui and his team compared the long-term survival of 963 pediatric patients, including 89 older adolescents, treated between 1991 and 2007 who were enrolled in 4 consecutive Total Therapy studies — studies XIIA, XIIB, XIV, and XV — that used protocols developed at St. Jude.
In the first 3 studies, treatment selection was based on presenting clinical features and leukemic cell genetics. In study XV, measuring the level of minimal residual disease (MRD) either by flow cytometry or polymerase chain reaction, was used to monitor the patient's response to and compliance with treatment, which featured intensive methotrexate, glucocorticoid, vincristine, and asparaginase, as well as early triple intrathecal therapy for higher-risk ALL.
In the Total XV study, any patient with 1% or more bone marrow MRD on day 19 of remission induction, or 0.1% to 0.99% MRD after completion of induction therapy, was considered to have standard-risk ALL. Patients who were unable to achieve morphologic remission or who had presence of MRD 1% or greater after completion of induction therapy and persistence of MRD 0.1% or greater beyond week 7 of continuation treatment were deemed to have high-risk ALL and became candidates for allogeneic stem cell transplantation.
The Total XV regimen also replaced radiation of the brain with intrathecal chemotherapy. Patients with low-risk disease received 13 to 18 intrathecal treatments, and patients with standard-risk disease received 16 to 25 intrathecal treatments. Prophylactic cranial irradiation was not used, as per the protocol of Total XV.
Survival Rate Increased Significantly With XV Protocol
In the earlier studies, the 5-year event-free survival rate and the 5-year overall survival rate for the 44 older adolescents were both 59.1% (95% confidence interval [CI], 43% - 72%). This was "strikingly" inferior to the event-free survival rate of 82.6% (95% CI, 78.5% - 86%; P < .001) and the overall survival rate of 88.3% (95% CI, 84.7% - 91.1%) achieved in the 403 younger patients, the investigators reported.
In contrast, in study XV, the 5-year event-free survival rates were 86.4% ± 5.2% (standard error) for the 45 older adolescents and 87.4% ± 1.7% for the 453 younger patients. The 5-year overall survival rates were 87.9% ± 5.1% for the older teenagers and 94.1% ± 1.2% for the younger patients.
In addition, patients treated in study XV were less likely to suffer serious late treatment effects, including second cancers and infertility. "Our patients had a good quality of life. We have followed them for over 10 years, and of the 500 patients, only one developed a secondary cancer," Dr. Pui noted. "This is the lowest for any protocol."
Dr. Pui also said that his study highlights the fact that good results in pediatric ALL can be achieved without the use of radiation. It also underlines the importance of personalizing therapy and being aware of compliance.
"We do not give everyone the same dose. Instead, we base the dose on individual pharmacokinetics and pharmacodynamics. We pay close attention to compliance. We monitor patients regularly, and we can tell who is not taking their oral medications. We counsel these patients until they become compliant, and we keep checking to make sure they stay compliant. This is very important, especially for the older teens," Dr. Pui said.
The study also reinforces the growing body of evidence that suggests older teenagers and even young adults with ALL do better on pediatric — as opposed to adult — protocols.
"Pediatric ALL specialists who treat adolescents love to see this kind of data get published," Susan Rheingold, MD, assistant professor of medicine at Children's Hospital of Philadelphia in Pennsylvania, told Medscape Medical News.
Studies have been showing since the early 2000s that older teenagers and young adults do better on pediatric protocols than adult protocols, she said. "In general, the pediatric protocols had a 65% 5-year cure rate, and the adult protocols had a 45% cure rate. When those results began to come out, pediatric oncologists started to say, 'We need to be treating these older adolescents. We need to be treating them like 10-year-olds, and not like 70-year-olds, so we can improve their cure rate. And when it's a 20% higher cure rate — that's significant," she said.
Dr. Rheingold noted that the protocols of the Children's Oncology Group are open to patients up to the age of 30 years.
"You don't stop being a child automatically at the age of 18. Our university hospital [University of Pennsylvania Medical Center] is hearing the message that pediatric oncologists are curing these young adult patients at higher rates with chemo and without transplants, and are sending us patients who are in their 20s," she said.
"The emergency rooms between the adult hospital and the pediatric hospital are probably no further than 100 feet apart. A 21-year-old can walk into either emergency room with a new diagnosis of leukemia, and you would hate to think that what door they chose to walk into could change their cure rate by 10% or 20%."
This research was supported in part by the National Institutes of Health, the American Cancer Society, and the American Lebanese Syrian Associated Charities. Dr. Pui and Dr. Rheingold have disclosed no relevant financial relationships.
RISE IN BREAST CANCER INCIDENCE IN UK
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Although breast cancer mortality continues to fall, the incidence of breast cancer is increasing in the United Kingdom; the latest estimate for lifetime risk is now 1 in 8 (up from 1 in 9 ten years ago).
This new estimate, from Cancer Research UK, was widely reported in the media, with headlines emphasizing the frightening statistic of 1 in 8, but few reports explained that risk increases sharply with age.
Breast cancer rates have risen by 3.5% in 10 years, the organization reported. A diagnosis of breast cancer was recorded in 47,700 women in 2008, compared with 42,400 women in 1999.
The biggest rise was among women 50 to 69 years of age, where the increase was more than 6% in that 10-year period. This age group represents almost half (48%) the total number of cases. Another 33% of cases were diagnosed in women older than 70 years of age.
Only 19% of the total cases were diagnosed in younger women (25 to 49 years); in this age group, the rate of breast cancer actually dropped slightly (by 0.5%).
According to Cancer Research UK, "there's no simple answer" to why breast cancer rates are increasing, but more cancers being detected by mammography screening, lifestyle changes such as increased alcohol use and obesity, an aftermath of prolonged use of hormone replacement therapy, women having fewer children and breastfeeding less, and the increasing age of the population are possible explanations.
Age in particular has a major effect. The risk for breast cancer increases sharply from around the time of the menopause and continues to rise with increasing age.
Risk for Breast Cancer by Age
All of these potential explanations, along with several others, are discussed in some detail on a science blog on the Cancer Research UK Web site.
Change in Mammography Policy
These latest figures chart a rise from 1999 to 2008, but about halfway through that period (in 2004), there was a change in national policy in the United Kingdom, when women 65 to 69 years of age started to be included in the national screening breast screening program. Before 2004, invitations for mammograms stopped when women reached 65 years of age (they start at 50 years).
The rise in breast cancer diagnoses in this age group probably coincides with this, according to the organization, because an increase in the number of women being screened would very likely lead to more cancers being detected.
Cancer Research UK acknowledges the controversy that has raged over mammography leading to the overdiagnosis of breast cancer, in particular the fact that it picks up cases of ductal carcinoma in situ (DCIS), which might never develop into a problem. "But our new analysis doesn't include cases of DCIS, so these noninvasive tumors can't explain the rising breast cancer rates in women aged 65 to 69," it reports.
Now for the Good News
"While it's worrying that women are now more likely to develop breast cancer than they were a decade ago, there is good news too," Cancer Research UK explains, pointing out that survival rates have "shot up."
"Almost 2 out of every 3 women with breast cancer now survive the disease beyond 20 years, compared with less than half in the 1990s. And more than three quarters of women diagnosed with breast cancer survive for at least 10 years, or more," it notes.
This new estimate, from Cancer Research UK, was widely reported in the media, with headlines emphasizing the frightening statistic of 1 in 8, but few reports explained that risk increases sharply with age.
Breast cancer rates have risen by 3.5% in 10 years, the organization reported. A diagnosis of breast cancer was recorded in 47,700 women in 2008, compared with 42,400 women in 1999.
The biggest rise was among women 50 to 69 years of age, where the increase was more than 6% in that 10-year period. This age group represents almost half (48%) the total number of cases. Another 33% of cases were diagnosed in women older than 70 years of age.
Only 19% of the total cases were diagnosed in younger women (25 to 49 years); in this age group, the rate of breast cancer actually dropped slightly (by 0.5%).
According to Cancer Research UK, "there's no simple answer" to why breast cancer rates are increasing, but more cancers being detected by mammography screening, lifestyle changes such as increased alcohol use and obesity, an aftermath of prolonged use of hormone replacement therapy, women having fewer children and breastfeeding less, and the increasing age of the population are possible explanations.
Age in particular has a major effect. The risk for breast cancer increases sharply from around the time of the menopause and continues to rise with increasing age.
Risk for Breast Cancer by Age
| Age (Years) | Risk |
| 29 | 1 in 2000 |
| 39 | 1 in 215 |
| 49 | 1 in 50 |
| 59 | 1 in 22 |
| 69 | 1 in 13 |
| Lifetime risk | 1 in 8 |
All of these potential explanations, along with several others, are discussed in some detail on a science blog on the Cancer Research UK Web site.
Change in Mammography Policy
These latest figures chart a rise from 1999 to 2008, but about halfway through that period (in 2004), there was a change in national policy in the United Kingdom, when women 65 to 69 years of age started to be included in the national screening breast screening program. Before 2004, invitations for mammograms stopped when women reached 65 years of age (they start at 50 years).
The rise in breast cancer diagnoses in this age group probably coincides with this, according to the organization, because an increase in the number of women being screened would very likely lead to more cancers being detected.
Cancer Research UK acknowledges the controversy that has raged over mammography leading to the overdiagnosis of breast cancer, in particular the fact that it picks up cases of ductal carcinoma in situ (DCIS), which might never develop into a problem. "But our new analysis doesn't include cases of DCIS, so these noninvasive tumors can't explain the rising breast cancer rates in women aged 65 to 69," it reports.
Now for the Good News
"While it's worrying that women are now more likely to develop breast cancer than they were a decade ago, there is good news too," Cancer Research UK explains, pointing out that survival rates have "shot up."
"Almost 2 out of every 3 women with breast cancer now survive the disease beyond 20 years, compared with less than half in the 1990s. And more than three quarters of women diagnosed with breast cancer survive for at least 10 years, or more," it notes.
DIET SODA INCREASES CARDIOVASCULAR RISK?
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Diet soda may not be the healthier alternative many had hoped. A new study suggests that the popular drinks may increase the risk for stroke, myocardial infarction, and vascular death.
"People who had diet soda every day experienced a 61% higher risk of vascular events than those who reported drinking no soda," lead investigator Hannah Gardener, ScD, an epidemiologist from the University of Miami Miller School of Medicine in Florida, told reporters attending a news conference here at the International Stroke Conference.
The risk persisted after controlling for metabolic syndrome, peripheral vascular disease, and cardiac disease history (relative risk, 1.48; 95% confidence interval, 1.03 - 2.12).
"This is the first report of this association," said American Stroke Association national spokesperson Larry Goldstein, MD. "I think that it's always good to do things in moderation. People should look at this information and consider it in the context of their other risk factors."
The researchers looked at more than 2500 people from the multiethnic Northern Manhattan Study. Participants were asked to report how much and what kind of soda they drank.
During an average follow-up of 9.3 years, 559 vascular events occurred, including ischemic and hemorrhagic stroke.
The researchers also observed a marginally significant increased risk for vascular events among those who consumed diet soda daily and regular soda once or more a month (adjusted relative risk, 1.74; 95% confidence interval, 0.96 - 3.16).
As reported by Medscape Medical News, previous studies have suggested a link between diet soda consumption and the risk for metabolic syndrome and diabetes. But this is the first time diet drinks have been associated with vascular events.
"This is an observational study and not a prospective randomized trial," Dr. Goldstein, from the Duke Stroke Center, in Durham, North Carolina, pointed out. "This is an association and not yet a proven causal relationship."
The investigators acknowledge that additional studies are needed. The potential mechanisms for the association between diet soda and vascular events remain unknown.
What should clinicians advise patients on the basis of the information we have today? Steven Greenberg, MD, from Harvard Medical School in Boston, Massachusetts, suggests that patients start by concentrating on a healthy diet and regular exercise. "Once the metabolic syndrome is under control and any risk of diabetes, then we can consider cutting back on soda consumption." Dr. Greenberg is the vice chair of the International Stroke Conference Committee, and during an interview he suggested that patients shouldn't rush to eliminate diet drinks.
"I do think this is a wake-up call, though," he said, "and we need to start paying closer attention."
This study was funded by the Javits award from the National Institute of Neurological Disorders and Stroke and the Evelyn McKnight Brain Institute. The researchers have disclosed no relevant financial relationships.
American Stroke Association International Stroke Conference. Abstract # P55. News conference February 9, 2011.
"People who had diet soda every day experienced a 61% higher risk of vascular events than those who reported drinking no soda," lead investigator Hannah Gardener, ScD, an epidemiologist from the University of Miami Miller School of Medicine in Florida, told reporters attending a news conference here at the International Stroke Conference.
The risk persisted after controlling for metabolic syndrome, peripheral vascular disease, and cardiac disease history (relative risk, 1.48; 95% confidence interval, 1.03 - 2.12).
"This is the first report of this association," said American Stroke Association national spokesperson Larry Goldstein, MD. "I think that it's always good to do things in moderation. People should look at this information and consider it in the context of their other risk factors."
The researchers looked at more than 2500 people from the multiethnic Northern Manhattan Study. Participants were asked to report how much and what kind of soda they drank.
During an average follow-up of 9.3 years, 559 vascular events occurred, including ischemic and hemorrhagic stroke.
The researchers also observed a marginally significant increased risk for vascular events among those who consumed diet soda daily and regular soda once or more a month (adjusted relative risk, 1.74; 95% confidence interval, 0.96 - 3.16).
As reported by Medscape Medical News, previous studies have suggested a link between diet soda consumption and the risk for metabolic syndrome and diabetes. But this is the first time diet drinks have been associated with vascular events.
"This is an observational study and not a prospective randomized trial," Dr. Goldstein, from the Duke Stroke Center, in Durham, North Carolina, pointed out. "This is an association and not yet a proven causal relationship."
The investigators acknowledge that additional studies are needed. The potential mechanisms for the association between diet soda and vascular events remain unknown.
What should clinicians advise patients on the basis of the information we have today? Steven Greenberg, MD, from Harvard Medical School in Boston, Massachusetts, suggests that patients start by concentrating on a healthy diet and regular exercise. "Once the metabolic syndrome is under control and any risk of diabetes, then we can consider cutting back on soda consumption." Dr. Greenberg is the vice chair of the International Stroke Conference Committee, and during an interview he suggested that patients shouldn't rush to eliminate diet drinks.
"I do think this is a wake-up call, though," he said, "and we need to start paying closer attention."
This study was funded by the Javits award from the National Institute of Neurological Disorders and Stroke and the Evelyn McKnight Brain Institute. The researchers have disclosed no relevant financial relationships.
American Stroke Association International Stroke Conference. Abstract # P55. News conference February 9, 2011.
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