Western Regional Blog – BC, YK, AB, NWT and Nunavut
Can the Preoperative HE4 Level Predict Optimal Cytoreduction in Patients With Advanced Ovarian Carcinoma?
Gynecol Oncol. 2012 Dec 7; [Epub Ahead of Print]
R Angioli, F Plotti, S Capriglione, et al
Objective: Optimal surgical outcome has been proved to be one of the most powerful survival determinants in the management of ovarian cancer patients. Actually, for ovarian cancer patients there is no general consensus on the preoperative establishment of cytoreducibility.
Methods: Between January 2011 and June 2012 patients affected by suspicious advanced ovarian cancer, referred to the Department of Gynecology of Campus Biomedico of Rome were enrolled in the study. All patients had serum CA125 and HE4 measured preoperatively. After a complete laparoscopy to assess the possibility of optimal debulking surgery defined as no visible residual tumor after cytoreduction (RT = 0), patients were submitted to primary cytoreductive surgery (Group A) or addressed to neoadjuvant chemotherapy (Group B).
Results: After diagnostic open laparoscopy, 36 patients underwent optimal primary cytoreductive surgery (Group A) and 21 patients were addressed to neoadjuvant chemotherapy (Group B). In our population, based on ROC curve, the HE4 value of 262 pmol/L is the best cut-off to identify patients candidates to optimal cytoreduction with a sensitivity of 86.1% and a specificity of 89.5% (PPV = 93.9 % and NPV = 77%). In addition, CA125 has a sensitivity of 58.3% and a specificity of 84% at cut-off of 414 UI/mL (AUC is 0.68, 95% C.I. = 0,620 to 0,861).
Conclusion: Our data indicate that preoperative HE4 is a better predictor for optimal cytoreduction compared to CA125. The best combination in predicting cytoreduction is HE4 ≤ 262 pmol/L and ascites < 500mL with a sensitivity of 100% and a specificity of 89.5% (PPV = 94% and NPV = 100%).
The results of a study Dr. Schrag and colleagues conducted on how patients with advanced cancer view their chemotherapy treatment in terms of expectations and understanding the purpose of the treatment were recently published in the New England Journal of Medicine.
Patient Expectations about Their Cancer Treatment
By Deborah Schrag, MD, MPH1 | December 20, 2012 Interviewed by Anna Azvolinsky, PhD
Cancer Network: Dr. Schrag, could you describe the design of the study and impetus and also the major questions it addressed?
Dr. Schrag: This was a survey of patients, a comprehensive survey of patients with newly diagnosed lung and colorectal cancer about many aspects of their treatment. The study was called Share Thoughts on Care, and it included patients, their caregivers, from multiple sites across the country—patients treated at the MACA, patients treated in managed care settings, for example, Kaiser. We included patients from North Carolina, California, really a broad class of patients. The goal was really to understand patients’ perceptions and viewpoints about what the experience of cancer is actually like. The question we focused on in this particular paper is patients’ expectations and understanding of the goal of chemotherapy treatment. Specifically, what patients’ expectations were about the likelihood that chemotherapy would provide them with benefit, specifically in terms of the likelihood of achieving a cure.
Cancer Network: What was the age range of the patients in the study? Were they mostly older patients?
Dr. Schrag: There was a range. The nice thing about this study is that it is really population based, so a nice sampling of what typical patients with these diseases, lung and colorectal cancer, would look like. It is really representative. There are younger patients and older patients, it really spans the spectrum.
Cancer Network: The study results showed that at least two-thirds of the more than 1,000 patients in the study believed that their chemotherapy treatment could cure them, is that correct? What were some of the other results you found?
Dr. Schrag: So, our most concerning finding is that there just seems to be a mismatch between expectations and reality. Patients did not recognize that chemotherapy is very unlikely to provide a cure. Some patients did understand correctly that chemotherapy is very unlikely to provide a cure in the context of stage IV diagnoses for these common cancers. But many patients, approximately two-thirds, did not recognize that. And that just suggests that there is a disconnect, a communication issue that we need to get a better handle on.
Cancer Network: Are there certain types of patients that your study suggests are more likely to be out of tune or are these miscommunication issues perhaps with their clinician? Is age a factor here?
Dr. Schrag: We looked at a whole number of factors and there were a few that seemed to make a difference, but curiously, age was not one. Colorectal cancer patients were a bit more likely to not understand that chemotherapy was unlikely to be curative compared to lung cancer patients. That was a factor—which type of cancer the patient had. There was a small trend that patients treated in integrated health networks systems, so managed care systems, seemed to be a bit more likely to have expectations that were better aligned with reality. Patients who belonged to a minority group or minority-ethnicity group also were a little bit more likely to not understand, to not have a good handle on realistic expectations about what chemotherapy can and can’t do.
Cancer Network: Do you think that the results reflect the status of the majority of advanced cancer patients throughout this country and perhaps, is this also a reflection of where the patient may be treated, at a community hospital versus an academic center for example?
Dr. Schrag: The real strength of the study is it included patients who were treated at both academic centers and community centers so I think that the finding is likely to be valid. In other words, if you went out today and repeated this study with a different sample of patients, you would find very much the same thing.
Cancer Network: What do you think the remedy is? Better communication on the side of the oncologist? Do you think that oncologists are not so willing to speak about the actual odds of the patients surviving for long with their advanced cancer?
Dr. Schrag: I think that our study finding really raises just how complicated an issue this is. This is not as simple as saying this is all the patient or all the physician. It is clearly some of both. It is possible for excellent clinicians to convey compassion and hope and provide realistic information about what chemotherapy can and cannot achieve to help patients make their decisions. But, clearly, sometimes this doesn’t happen. Sometimes people just have expectations that are just not well aligned with reality. And we need to look at this more carefully. We need to think about strategies to improve communication. Sometimes it may be that physicians are hoping for the best possible outcome that may be related to issues such as framing. “Here is what is possible” is very different than “here is what is probable.” It is certainly reasonable to give patients information about what may happen, the best-case scenario, if you will. But people also need information about what is most likely to happen. I don’t think it is that physicians are being dishonest with their patients. It may be sort of framing, trying to convey hope and be compassionate and supportive at the same time they are trying to deliver very difficult news and difficult information to deliver and harder still to hear.
Cancer Network: There have been studies showing that many terminal cancer patients receive aggressive, and often times expensive, treatments very close to their time of death from cancer. Do your results perhaps suggest that with better communication between clinicians and patients and their families, patients and their families will be able to better understand the odds of such treatment succeeding and perhaps opt for palliative and hospice care earlier in the course of their advanced disease?
Dr. Schrag: We can’t say that that will happen for sure, we don’t know that. But I think that is certainly a possibility. You know, patients might make the same decisions about receiving their chemotherapy or they may make different decisions, but I think it is really that we need to figure out a way to convey information, even difficult information effectively, and we need to do a better job. And that probably involves helping both physicians and patients. I think it is possible to teach communication skills. It is also possible to not put all of the pressure on the doctor–patient relationship. We usually treat patients in the context of complicated healthcare settings where there are multiple members of the team—chemotherapy nurse at a minimum, but often a social worker, and other caregivers. So there are alternative ways to communicate and team members can really work together to help make sure patients have all of the information they need to make good decisions. Could that potentially help us cut down on chemotherapy very close to end of life among patients whose overall functional status and quality of life is so limited that they are unlikely to derive benefit from the treatment? I think that is absolutely a possibility.
Cancer Network: Anything else you would like to highlight about the results or maybe of follow-up studies that are ongoing?
Dr. Schrag: Yes, I think that follow-up studies are really trying to figure out what we can do to intervene to improve upon this situation and help make sure that patients and physicians are making informed decisions, and that is really challenging. And we need to do that without taking away people’s hopes, without making people feel that they received a devastating diagnosis and that there are no options, that is clearly counterproductive and not the case. But getting people good information, and then letting them make the best decisions for them is critical. I think the Patients’ Center Outcomes Research Institute is really focusing millions of dollars on making research grant opportunities available. We and others are competing for some of those awards to try to try to figure out how we can do better at this.
Patients’ expectations about effects of chemotherapy for advanced cancer.
Weeks JC, Catalano PJ, Cronin A, Finkelman MD, Mack JW, Keating NL, Schrag D.
N Engl J Med. 2012 Oct 25;367(17):1616-25. doi: 10.1056/NEJMoa1204410.
BACKGROUND: Chemotherapy for metastatic lung or colorectal cancer can prolong life by weeks or months and may provide palliation, but it is not curative.
METHODS: We studied 1193 patients participating in the Cancer Care Outcomes Research and Surveillance (CanCORS) study (a national, prospective, observational cohort study) who were alive 4 months after diagnosis and received chemotherapy for newly diagnosed metastatic (stage IV) lung or colorectal cancer. We sought to characterize the prevalence of the expectation that chemotherapy might be curative and to identify the clinical,
might be curative and to identify the clinical, sociodemographic, and health-system factors associated with this expectation. Data were obtained from a patient survey by professional interviewers in addition to a comprehensive review of medical records.
RESULTS: Overall, 69% of patients with lung cancer and 81% of those with colorectal cancer did not report understanding that chemotherapy was not at all likely to cure their cancer. In multivariable logistic regression, the risk of reporting inaccurate beliefs about chemotherapy was higher among patients with colorectal cancer, as compared with those with lung cancer (odds ratio, 1.75; 95% confidence interval [CI], 1.29 to 2.37); among nonwhite and Hispanic patients, as compared with non-Hispanic white patients (odds ratio for Hispanic patients, 2.82; 95% CI, 1.51 to 5.27; odds ratio for black patients, 2.93; 95% CI, 1.80 to 4.78); and among patients who rated their communication with their physician very favorably, as compared with less favorably (odds ratio for highest third vs. lowest third, 1.90; 95% CI, 1.33 to 2.72). Educational level, functional status, and the patient’s role in decision making were not associated with such inaccurate beliefs about chemotherapy.
CONCLUSIONS: Many patients receiving chemotherapy for incurable cancers may not understand that chemotherapy is unlikely to be curative, which could compromise their ability to make informed treatment decisions that are consonant with their preferences. Physicians may be able to improve patients’ understanding, but this may come at the cost of patients’ satisfaction with them. (Funded by the National Cancer Institute and others.)
The lead researcher on the study, Professor Nazneen Rahman, said it was one of her lab’s “most interesting and exciting discoveries”. According to the study, published in the journal Nature, women with faults in a gene called PPM1D in their blood cells were 20 per cent more likely to develop breast or ovarian cancer. That is twice the average breast cancer risk and more than 10 times the ovarian cancer risk of women in the general population.
Blood cell gene fault linked to breast and ovarian cancer
Scientists have linked a rare genetic fault in the immune system to an increased risk of breast and ovarian cancers.
The research from a team at The Institute of Cancer Research suggests an entirely new way tumours develop.
The lead researcher on the study, Professor Nazneen Rahman, said it was one of her lab’s “most interesting and exciting discoveries”.
According to the study, published in the journal Nature, women with faults in a gene called PPM1D in their blood cells were 20 per cent more likely to develop breast or ovarian cancer.
That is twice the average breast cancer risk and more than 10 times the ovarian cancer risk of women in the general population.
The discovery could have implications for future genetic testing and targeted prevention, especially in the case of ovarian cancer.
Dr Emma Smith, Cancer Research UK’s senior science information officer said: “This exciting discovery could help doctors identify women at higher risk of developing breast and ovarian cancer in the future.
“This may have a particular impact on ovarian cancer, which is often diagnosed at a late stage.
“Understanding the genetic mistakes that drive these cancers may also lead to new ways to treat these diseases.”
The researchers speculate that they have uncovered a new cancer-causing process, since the PPM1D gene appears to operate differently to other genes known to increase the risk of breast and ovarian cancer, such as BRCA1 and BRCA2.
The team found that changes in PPM1D were not inherited and rather than being present in every cell – as in most inherited cancer-causing genes – they were only present in immune cells known as lymphocytes.
Even more surprisingly, the PPM1D gene was not altered in women’s cancer cells, nor in their normal breast or ovarian cells, the study discovered.
The changes make the PPM1D gene overactive, reducing the action of a gene called TP53, one of the most frequently altered genes in cancer cells.
The ICR’s Professor Nazneen Rahman, who led the study, said: “This is one of our most interesting and exciting discoveries. At every stage the results were different from the accepted theories.
“We don’t yet know exactly how PPM1D mutations are linked to breast and ovarian cancer, but this finding is stimulating radical new thoughts about the way genes and cancer can be related.”
Professor Rahman said the findings could also help inform women’s decisions about future medical treatments.
A woman might, for example, consider keyhole surgery to remove her ovaries after completing her family if she knew she had PPM1D changes and had a one in five chance of developing ovarian cancer.
The study was funded by Cancer Research UK, the ICR, the Wellcome Trust and Breakthrough Breast Cancer.
Researchers analysed 507 genes involved in DNA repair in 1,150 women with breast or ovarian cancer, identifying PPM1D gene changes in five women.
They then sequenced the PPM1D gene in 7,781 women with breast or ovarian cancer and 5,861 people from the general population.
25 of the women with cancer had faults in PPM1D, compared with only one in the general population, a highly statistically significant difference, the researchers said.
Copyright Press Association 2012
Nature. 2012 Dec 16. doi: 10.1038/nature11725. [Epub ahead of print]
Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer.
Ruark E, Snape K, Humburg P, Loveday C, Bajrami I, Brough R, Rodrigues DN, Renwick A, Seal S, Ramsay E, Duarte SD, Rivas MA, Warren-Perry M, Zachariou A, Campion-Flora A, Hanks S, Murray A, Pour NA, Douglas J, Gregory L, Rimmer A, Walker NM, Yang TP, Adlard JW, Barwell J, Berg J, Brady AF, Brewer C, Brice G, Chapman C, Cook J, Davidson R, Donaldson A, Douglas F, Eccles D, Evans DG, Greenhalgh L, Henderson A, Izatt L, Kumar A, Lalloo F, Miedzybrodzka Z, Morrison PJ, Paterson J, Porteous M, Rogers MT, Shanley S, Walker L, Gore M, Houlston R, Brown MA, Caufield MJ, Deloukas P, McCarthy MI, Todd
JA; The Breast and Ovarian Cancer Susceptibility Collaboration; Wellcome Trust Case Control Consortium, Turnbull C, Reis-Filho JS, Ashworth A, Antoniou AC, Lord CJ, Donnelly P, Rahman N.
Improved sequencing technologies offer unprecedented opportunities for investigating the role of rare genetic variation in common disease. However, there are considerable challenges with respect to study design, data analysis and replication. Using pooled next-generation sequencing of 507 genes implicated in the repair of DNA in 1,150 samples, an analytical strategy focused on protein-truncating variants (PTVs) and a large-scale sequencing case-control replication experiment in 13,642 individuals, here we show that rare PTVs in the p53-inducible protein phosphatase PPM1D are associated with predisposition to breast cancer and ovarian cancer. PPM1D PTV mutations were present in 25 out of 7,781 cases versus 1 out of 5,861 controls (P = 1.12 × 10(-5)), including 18 mutations in 6,912 individuals with breast cancer (P = 2.42 × 10(-4)) and 12 mutations in 1,121 individuals with ovarian cancer (P = 3.10 × 10(-9)). Notably, all of the identified PPM1D PTVs were mosaic in lymphocyte DNA and clustered within a 370-base-pair region in the final exon of the gene, carboxy-terminal to the phosphatase catalytic domain. Functional studies demonstrate that the mutations result in enhanced suppression of p53 in response to ionizing radiation exposure, suggesting that the mutant alleles encode hyperactive PPM1D isoforms. Thus, although the mutations cause premature protein truncation, they do not result in the simple loss-of-function effect typically associated with this class of variant, but instead probably have a gain-of-function effect. Our results have implications for the detection and management of breast and ovarian cancer risk. More generally, these data provide new insights into the role of rare and of mosaic genetic variants in common conditions, and the use of sequencing in their identification.
“TAKE-HOME MESSAGE – A case-controlled retrospective review found that intake of metformin by patients with ovarian cancer independently predicted better survival.”
Metformin Intake is Associated With Better Survival in Ovarian Cancer: A Case-Control Study
Cancer. 2012 Dec 3;[Epub Ahead of Print], S Kumar, A Meuter, P Thapa, et al
Background: The objective of this case-control study was to identify any association of metformin intake with the survival of patients with ovarian cancer.
Methods: In this retrospective case-control study, women with ovarian cancer who received metformin (cases) were compared with women with ovarian cancer who did not receive metformin (controls). A 2-layered analysis was conducted. In preliminary analysis, all cases (the OC cohort) were compared with controls at a 1:2 ratio. Subsequently, in definitive analysis, only patients who had epithelial ovarian cancer (the EOC cohort) were compared with controls at a 1:3 ratio. In the EOC cohort, cases were matched with controls for age (±5 years), International Federation of Gynecology and Obstetrics stage, and residual disease. Prognostic variables and disease specific survival were compared using chi-square tests, the Kaplan-Meier (log-rank) method, and Cox proportional hazards analysis.
Results: In a preliminary analysis of the OC cohort (72 cases and 143 controls), cases had better survival (5-year disease-specific survival for cases vs controls, 73% vs 44%; P = .0002). In the definitive analysis of the EOC cohort (61 cases and 178 controls), the distribution of age, disease stage, optimal cytoreduction, serous histology, and platinum chemotherapy remained similar between cases and controls (P > .05). Despite these similarities, cases had significantly better survival (5-year disease-specific survival for cases vs controls, 67% vs 47%; P = .007). On multivariate analysis, metformin remained an independent predictor of survival (hazard ratio, 2.2; 95% confidence interval, 1.2-3.8; P = .007) after controlling for disease stage, grade, histology, chemotherapy, body mass index, and surgical cytoreduction.
Conclusions: The results of this study indicated an association of metformin intake with survival in patients with ovarian cancer. The receipt of metformin was associated with better survival, and the authors concluded that metformin is worthy of clinical trials in ovarian cancer.
Cancer and diabetes are two leading killers in America, and while each can be a devastating diagnosis, researchers are finding that the two often occur together.
Juggling Diabetes and Cancer
By ANAHAD O’CONNOR; December 31, 2012, 4:40 pm
Nine years ago, Brenda Gray, a former schoolteacher in North Carolina, discovered she had Type 2 diabetes.
Since then, she has learned to manage the disease, diligently taking her medicine and keeping tabs on her blood sugar. But in September, she was told she had skin cancer, and her diabetes spun out of control.
Ms. Gray started an aggressive course of treatment that included radiation therapy. But the treatments weakened her and destroyed her appetite. Unable to eat, she developed dangerously low blood-sugar levels, and about two months ago, Ms. Gray’s daughter had to rush her to a hospital.
“She found me in bed shaking and sweating,” said Ms. Gray, who is 62 and lives in Durham. “When I got to the hospital, they couldn’t understand how I was still standing.”
Cancer and diabetes are two of the leading killers in America. Each can be a devastating diagnosis in its own right, but researchers are finding that the two often occur together. By some estimates, as many as one in five cancer patients also has diabetes.
In a recent joint report, the American Cancer Society and the American Diabetes Association noted that people with Type 2 diabetes have an increased risk of developing cancers of the liver, pancreas, colon and bladder. Researchers with the National Cancer Institute released a similar report last year, which found greater rates of cancer among diabetics, as well as an elevated risk of dying from cancer.
Experts say it is clear from accumulating clinical data that the two share some biological links. The problem results from simple demographics as well: with the rapid rise in Type 2 diabetes and a growing population of cancer survivors, the two diseases are coinciding more frequently in older patients.
“We are going to see a lot greater numbers of people with both diseases,” said Edward Giovannucci, a professor of nutrition and epidemiology at the Harvard School of Public Health and an author of the joint report. “By some estimates, the link between diabetes and cancer may quantitatively become even more important than the link between smoking and cancer.”
Already, oncologists say, it is not uncommon to encounter patients struggling to balance cancer treatments with insulin shots and diabetes drugs. Because cancer is generally seen as the more lethal of the two diseases, patients often make it the priority.
“Although cancer is no longer generally a death sentence, for many patients, they see it as that no matter what you say,” said Dr. June McKoy, a geriatric oncologist at the Northwestern University Feinberg School of Medicine. “Suddenly, they put their diabetes on the back burner, and they focus on the cancer.” But high blood sugar can damage kidneys and blood vessels, strain the immune system and worsen cancer prognosis.
Researchers say that the link between the two diseases is complex and driven by many factors. Typically, though, it is diabetes that sets the stage for cancer. “Most cancers don’t cause diabetes,” said Dr. Pankaj Shah, an endocrinologist at the Mayo Clinic in Rochester, Minn. “Mostly diabetes increases the risk of cancer.”
Type 2 diabetes is often preceded by chronically high insulin levels and high blood sugar, fertile conditions for cancer. Insulin is known to fuel cell growth, and cancer cells consume glucose out of proportion to other nutrients. The two diseases share many risk factors as well, including obesity, poor diet, physical inactivity, smoking and advanced age.
Another factor that complicates the relationship is the treatments given to patients. Diabetes drugs can have an impact on cancer prognosis and vice versa. Type 2 diabetics treated with the drug metformin, for example, develop cancer less frequently than diabetics given other medications. A number of clinical trials are now under way to see how well the drug performs as a cancer treatment.
Drugs used against cancer, on the other hand, tend to worsen diabetes. Chemotherapy can wreak havoc on blood sugar levels, and glucocorticoids, which are widely prescribed to alleviate nausea in cancer patients, promote insulin resistance, said Dr. Lorraine L. Lipscombe of Women’s College Hospital in Toronto.
Dr. Lipscombe was the lead author of a large study last month that found that breast cancer survivors were 20 percent more likely to receive a diabetes diagnosis than other women. The study found evidence that glucocorticoids and chemotherapy may hasten the onset of diabetes.
“They don’t cause diabetes in everyone, but they can bring out or unmask it in people who might already be vulnerable,” she said.
For diabetics who are used to tightly monitoring their blood sugar levels, the impact of cancer drugs can be alarming. Rigoberto Cortes, 71, a former metal worker in Chicago, has had Type 2 diabetes for over two decades. A year ago, he was told he had Stage 3 colon cancer.
“When I started chemotherapy, my sugar level was going way up and way down like never before,” he said. “I kept asking my oncologist what I should do.”
Mr. Cortes said his oncologist was not very concerned by the blood sugar swings. He eventually got a second opinion and switched doctors. He also lost weight and changed his eating habits, which helped minimize his blood sugar swings.
Although every case is different, the general strategy in treating such patients should be to get the cancer under control first, said Dr. Shah at the Mayo Clinic.
“Diabetes treatment essentially is given to prevent long-term complications,” he added.
At some hospitals, oncologists may take responsibility for managing blood sugar and other diabetes concerns in their cancer patients. But ideally, treatments should be coordinated by a team that includes a certified diabetes educator.
“They go over diet with the patient, review their medication, review their insulin,” said Dr. McKoy of Northwestern. “They can play a big role.”
For a diabetic trying to navigate the world of cancer, or a cancer patient navigating the world of diabetes, such interventions can be crucial. In a study published in October, Dr. McKoy and her colleagues looked at several years of health records for over 200,000 people with Type II diabetes who developed cancer.
Those who underwent a diabetes counseling session after their cancer diagnosis — consisting of two sessions a week for four to six weeks — were more likely to receives tests of hemoglobin A1c levels, a barometer of how well blood sugar has been controlled over time, and to take care of their blood sugar levels. As a result, they had fewer emergency room visits, fewer hospital admissions and lower health care costs.
Ms. Gray, the former schoolteacher in Durham, learned this firsthand. After her recent emergency, she worked with a diabetes educator at Duke University Hospital. Ms. Gray learned tips and strategies to balance the two diseases, including ways to keep her blood sugar normal when cancer treatments ruin her appetite.
“I came into the hospital and they got me back on track,” she said. “I was just so focused on the cancer. It changed everything. But I’ve learned how to face this.”
“TAKE-HOME MESSAGE – Study results of women with invasive ovarian cancer indicated that a BRCA mutation was associated with a better prognosis at 3 years but not at 10 years, suggesting no associated long-term survival benefit.”
Long-Term Ovarian Cancer Survival Associated With Mutation in BRCA1 or BRCA2
J Natl Cancer Inst. 2012 Dec 20;[Epub Ahead of Print], JR McLaughlin, B Rosen, J Moody, et al
Background: Studies have suggested that the 5-year survival of women with ovarian cancer and a BRCA1 or BRCA2 mutation is better than expected. We sought to evaluate the impact of carrying a BRCA1 or BRCA2 mutation on long-term survival of women after a diagnosis of invasive ovarian cancer.
Methods: One thousand six hundred twenty-six unselected women diagnosed with invasive ovarian cancer in Ontario, Canada, or in Tampa, Florida, between 1995 and 2004 were followed for a mean of 6.9 years (range = 0.3 to 15.7 years). Mutation screening for BRCA1 and BRCA2 revealed mutations in 218 women (13.4%). Left-truncated survival analysis was conducted to estimate ovarian cancer–specific survival at various time points after diagnosis for women with and without mutations.
Results: In the 3-year period after diagnosis, the presence of a BRCA1 or BRCA2 mutation was associated with a better prognosis (adjusted hazard ratio = 0.68, 95% confidence interval [CI] = 0.48 to 0.98; P = .03), but at 10 years after diagnosis, the hazard ratio was 1.00 (95% CI = 0.83 to 1.22; P = .90). Among women with serous ovarian cancers, 27.4% of women who were BRCA1 mutation carriers, 27.7% of women who were BRCA2 carriers, and 27.1% of women who were noncarriers were alive at 12 years past diagnosis.
Conclusion: For women with invasive ovarian cancer, the short-term survival advantage of carrying a BRCA1 or BRCA2 mutation does not lead to a long-term survival benefit
“This declining trend foreshadows a future negative impact on mortality from cancers of the breast, and cervix as well as increased morbidity associated with a later diagnosis of prostate cancer,” the study authors conclude.
US Cancer Screening Rates Fall in the Last Decade
Laurie Barclay, MD, Dec 28, 2012
In the last decade, the general US population did not meet Healthy People 2010 (HP2010) goals for cancer screening except for colorectal cancer, according to results from a US survey published online December 27 in Frontiers in Cancer Epidemiology and Prevention. However, cancer survivors met goals for all cancer types except cervical cancer.
“There is a great need for increased cancer prevention efforts in the U.S., especially for screening as it is considered one of the most important preventive behaviors and helps decrease the burden of this disease on society in terms of quality of life, the number of lives lost and insurance costs,” lead author Tainya C. Clarke, MPH, a research associate in the Department of Epidemiology and Public Health at the University of Miami, Miller School of Medicine, Florida, said in a news release.
“But despite this, our research has shown that adherence rates for cancer screenings have generally declined with severe implications for the health outlook of our society,” Dr. Clarke said.
Despite earlier diagnoses and more effective treatments prolonging survival, cancer is still a leading cause of death and a highly prevalent chronic disease. In 2011, cancer-related deaths in the United States exceeded 570,000.
The objective of this study was to analyze 10-year trends in adherence to screening for site-specific cancers as recommended by the American Cancer Society, using the HP2010 goals as an adherence measure. Participants were 174,393 adults at least 18 years of age who completed the National Health Interview Survey between 1997 and 2010 for whom detailed cancer screening information was available.
The investigators also analyzed data from 7528 working cancer survivors representing 3.8 million US workers, as well as data from 119,374 adults representing more than 100 million working Americans with no history of cancer.
The US population slightly exceeded the HP2010 goal for colorectal screening, with 54.6% of the general public having colorectal screening compared with the HP2010 goal of 50%. However, the general US population surveyed failed to meet HP2010 goals for recommended breast, cervical, and prostate cancer screening.
Cervical cancer screening rate was higher in women aged 21 years and older than in those aged 18 years and older, suggesting that increasing human papillomavirus vaccination may contribute to decreasing Papanicolaou tests. The proportion of men older than 50 years receiving prostate-specific antigen (PSA)
screening decreased by nearly 20% from 1999 to 2010, which the investigators suggest might reflect questions being raised about the effectiveness of PSA screening.
In contrast to the overall population, cancer survivors met and maintained the HP2010 goal for cancer screening at all sites with the exception of screening for cervical cancer, which decreased to 78% during the last decade. Compared with the general population, cancer survivors had higher screening rates, but there was a decline among cancer survivors who took part in cancer screenings during the last 3 years. Screening rates among cancer survivors were higher for those employed in white-collar and service occupations than for those employed in blue-collar occupations.
Study Limitations and Implications
Cancer survivors report “higher screening rates than the general population,” the study authors write. “Nevertheless, national screening rates are lower than desired, and disparities exist by cancer history and occupation. Understanding existing disparities, and the impact of cancer screening on survivors is crucial as the number of working survivors increases.”
Limitations of this study include a reliance on self-report for the main outcome variables, that the sample size of cancer survivors employed in the farming sector was too small for analysis, and a lack of data on what type of Papanicolaou test (liquid-based or glass smear) was performed on women screened for cervical cancer.
“This declining trend foreshadows a future negative impact on mortality from cancers of the breast, and cervix as well as increased morbidity associated with a later diagnosis of prostate cancer,” the study authors conclude. “Disagreements among the [US Preventive Services Task Force], the [American Cancer Society] and other recommending bodies over cancer screening guidelines may have contributed to the decline in screening throughout the decade. A decline in worker insurance rates over the decade under study could also be a contributing factor.”
This study was supported by a National Cancer Institute fellowship at the National Institutes of Health and the National Institute for Occupational Safety and Health. The authors have disclosed no relevant financial relationships.
Front Oncol. Published online December 27, 2012. Full text
The presence of genetic material from two other cancers in Pap smears, used to detect cervical cancer, suggests it may become possible to look for three diseases with one test.
Pap Test Could Help Find Cancers of Uterus and Ovaries
By DENISE GRADY
Published: January 9, 2013
For the first time, researchers have found genetic material from uterine or ovarian cancers in Pap smears, meaning that it may become possible to detect three diseases with just one routine test.
But the research is early, years away from being used in medical practice, and there are caveats. The women studied were already known to have cancer, and while the Pap test found 100 percent of the uterine cancers, it detected only 41 percent of the ovarian cancers. And the approach has not yet been tried in women who appear healthy, to determine whether it can find early signs of uterine or ovarian cancer.
On the other hand, even a 41 percent detection rate would be better than the status quo in ovarian cancer, particularly if the detection extends to early stages. The disease is usually advanced by the time it is found, and survival rates are poor. About 22,280 new cases were expected in the United States in 2012, and 15,500 deaths. Improved tests are urgently needed.
Uterine cancer has a better prognosis, but still kills around 8,000 women a year in the United States.
These innovative applications of the Pap test are part of a new era in which advances in genetics are being applied to the detection of a wide variety of cancers or precancerous conditions. Scientists are learning to find minute bits of mutant DNA in tissue samples or bodily fluids that may signal the presence of hidden or incipient cancers.
Ideally, the new techniques would find the abnormalities early enough to cure the disease or even prevent it entirely. But it is too soon to tell.
“Is this the harbinger of things to come? I would answer yes,” said Dr. Bert Vogelstein, director of the Ludwig Center for Cancer Genetics and Therapeutics at Johns Hopkins University, and a senior author of a report on the Pap test study published on Wednesday in the journal Science Translational Medicine. He said the genomes of more than 50 types of tumors had been sequenced, and researchers were trying to take advantage of the information.
Similar studies are under way or are being considered to look for mutant DNA in blood, stool, urine and sputum, both to detect cancer and also to monitor the response to treatment in people known to have the disease.
But researchers warn that such tests, used for screening, can be a double-edged sword if they give false positive results that send patients down a rabbit hole of invasive tests and needless treatments. Even a test that finds only real cancers may be unable to tell aggressive, dangerous ones apart from indolent ones that might never do any harm, leaving patients to decide whether to watch and wait or to go through surgery, chemotherapy and radiation with all the associated risks and side effects.
“Will they start recovering mutations that are not cancer-related?” asked Dr. Christopher P. Crum, a professor at Harvard Medical School who was not involved in the research.
But he also called the study a “great proof of principle,” and said, “Any whisper of hope to women who suffer from endometrial or ovarian cancer would be most welcome.”
DNA testing is already performed on samples from Pap tests, to look for the human papillomavirus, or HPV, which causes cervical cancer. Dr. Vogelstein and his team decided to try DNA testing for cancer. They theorized that cells or DNA shed from cancers of the ovaries and the uterine lining, or endometrium, might reach the cervix and turn up in Pap smears.
The team picked common mutations found in these cancers, and looked for them in tumor samples from 24 women with endometrial cancer and 22 with ovarian cancer. All the cancers had one or more of the common mutations.
Then, the researchers performed Pap tests on the same women, and looked for the same DNA mutations in the Pap specimens. They found the mutations in 100 percent of the women with endometrial cancer, but in only 9 of the 22 with ovarian cancer. The test identified two of the four ovarian cancers that had been diagnosed at an early stage.
Finally, the team developed a test that would look simultaneously for cancer-associated mutations in 12 different genes in Pap samples. Used in a control sample of 14 healthy women, the test found no mutations — meaning no false-positive results.
Dr. Luis A. Diaz, the other senior author of the report and an associate professor of oncology at Johns Hopkins, called the research a step toward a screening test that at first blush appears very effective at detecting endometrial cancer, though obviously less so at finding ovarian cancer.
“Probably one of the most exciting features of this approach,” Dr. Diaz said, “is that we wanted a test that would seamlessly integrate with routine medical practice that could be utilized with the same test that women get every day all over the world, the Pap smear.”
But, he added: “We can’t say it’s ready for prime time. Like all good science, it needs to be validated.”
He and other members of the team said it might be possible to improve the detection rate for ovarian cancer by looking for more mutations and by changing the technique of performing Pap tests to increase the likelihood of capturing cells from the ovary. The change might involve timing the test to a certain point in a woman’s monthly cycle, using a longer brush to collect cells from deeper within the cervix or prescribing a drug that would raise the odds of cells being shed from the ovary.
The technique also needs to be tested in much larger groups of women, including healthy ones, to find out whether it works, particularly at finding cancers early enough to improve survival. And studies must also find out whether it generates false positive results, or identifies cancers that might not actually need to be treated.
Michael H. Melner, a program director in molecular genetics and biochemistry for the American Cancer Society, called the research “very promising,” in part because it is based on finding mutations.
“It tells you not just that cancer is there, but which mutation is there,” Dr. Melner said. “As we learn more and more about which mutations are associated with more or less severe forms of cancer, it’s more information, and possibly more diagnostic.”
“Highlights – ► Platinum based doublets are the standard of care for patients with recurrent cervical cancer, although clinical benefit is limited. ► Clinical trial participation should be encouraged in order to determine potentially more efficacious regimens.”
Chemotherapy for Advanced and Recurrent Cervical Carcinoma: Results From Cooperative Group Trials
Gynecol Oncol. 2012 Dec 30;[Epub Ahead of Print], CA Leath, JM Straughn
Objective: To review the clinical trial experience with chemotherapy for patients with primary Stage IVB, persistent and recurrent cervical cancer.
Methods: Pubmed and cooperative group website search was performed and included clinical trials until September 2012. Emphasis was placed on the phase II and III clinical trial experience of the Gynecologic Oncology Group.
Results: Experience and trial results with single agents and combination agents in phase II settings are reviewed. Cisplatin has been considered the most effective agent for metastatic cervical cancer. Most patients who develop metastatic disease have received cisplatin with concurrent radiation and may no longer be sensitive to single-agent therapy. Therefore, cisplatin-based combination chemotherapy regimens have been extensively studied and eight sentinel phase III trials are discussed in this review.
Conclusion: Based on phase III results, the combination of cisplatin and paclitaxel remains the standard of care; however, alternative combination therapies including cisplatin/topotecan and cisplatin/gemcitabine may be acceptable considerations for patients when considering potential toxicities. Further research is necessary to determine the optimal therapy for this group of patients. Final data from GOG 240 and JCOG 0505 will likely contribute to the design of future clinical trials in this disease setting.
“Watson, 84, taught a course on cancer at Harvard University in 1959, three years before he shared the Nobel Prize in medicine for his role in discovering the double helix, which opened the door to understanding the role of genetics in disease.”
DNA pioneer James Watson takes aim at “cancer establishments”
Wed, Jan 09 06:34 AM EST
By Sharon Begley
NEW YORK (Reuters) – A day after an exhaustive national report on cancer found the United States is making only slow progress against the disease, one of the country’s most iconic – and iconoclastic – scientists weighed in on “the war against cancer.” And he does not like what he sees.
James Watson, co-discoverer of the double helix structure of DNA, lit into targets large and small. On government officials who oversee cancer research, he wrote in a paper published on Tuesday in the journal Open Biology, “We now have no general of influence, much less power … leading our country’s War on Cancer.”
On the $100 million U.S. project to determine the DNA changes that drive nine forms of cancer: It is “not likely to produce the truly breakthrough drugs that we now so desperately need,” Watson argued. On the idea that antioxidants such as those in colorful berries fight cancer: “The time has come to seriously ask whether antioxidant use much more likely causes than prevents cancer.”
That Watson’s impassioned plea came on the heels of the annual cancer report was coincidental. He worked on the paper for months, and it represents the culmination of decades of thinking about the subject. Watson, 84, taught a course on cancer at Harvard University in 1959, three years before he shared the Nobel Prize in medicine for his role in discovering the double helix, which opened the door to understanding the role of genetics in disease.
Other cancer luminaries gave Watson’s paper mixed reviews.
“There are a lot of interesting ideas in it, some of them sustainable by existing evidence, others that simply conflict with well-documented findings,” said one eminent cancer biologist who asked not to be identified so as not to offend Watson. “As is often the case, he’s stirring the pot, most likely in a very productive way.”
There is wide agreement, however, that current approaches are not yielding the progress they promised. Much of the decline in cancer mortality in the United States, for instance, reflects the fact that fewer people are smoking, not the benefits of clever new therapies.
“The great hope of the modern targeted approach was that with DNA sequencing we would be able to find what specific genes, when mutated, caused each cancer,” said molecular biologist Mark Ptashne of Memorial Sloan-Kettering Cancer Center in New York. The next step was to design a drug to block the runaway proliferation the mutation caused.
But almost none of the resulting treatments cures cancer. “These new therapies work for just a few months,” Watson told Reuters in a rare interview. “And we have nothing for major cancers such as the lung, colon and breast that have become metastatic.”
The main reason drugs that target genetic glitches are not cures is that cancer cells have a work-around. If one biochemical pathway to growth and proliferation is blocked by a drug such as AstraZeneca’s Iressa or Genentech’s Tarceva for non-small-cell lung cancer, said cancer biologist Robert Weinberg of MIT, the cancer cells activate a different, equally effective pathway.
That is why Watson advocates a different approach: targeting features that all cancer cells, especially those in metastatic cancers, have in common.
One such commonality is oxygen radicals. Those forms of oxygen rip apart other components of cells, such as DNA. That is why antioxidants, which have become near-ubiquitous additives in grocery foods from snack bars to soda, are thought to be healthful: they mop up damaging oxygen radicals.
That simple picture becomes more complicated, however, once cancer is present. Radiation therapy and many chemotherapies kill cancer cells by generating oxygen radicals, which trigger cell suicide. If a cancer patient is binging on berries and other antioxidants, it can actually keep therapies from working, Watson proposed.
“Everyone thought antioxidants were great,” he said. “But I’m saying they can prevent us from killing cancer cells.”
Research backs him up. A number of studies have shown that taking antioxidants such as vitamin E do not reduce the risk of cancer but can actually increase it, and can even shorten life. But drugs that block antioxidants – “anti-antioxidants” – might make even existing cancer drugs more effective.
Anything that keeps cancer cells full of oxygen radicals “is likely an important component of any effective treatment,” said cancer biologist Robert Benezra of Sloan-Kettering.
Watson’s anti-antioxidant stance includes one historical irony. The first high-profile proponent of eating lots of antioxidants (specifically, vitamin C) was biochemist Linus Pauling, who died in 1994 at age 93. Watson and his lab mate, Francis Crick, famously beat Pauling to the discovery of the double helix in 1953.
One elusive but promising target, Watson said, is a protein in cells called Myc. It controls more than 1,000 other molecules inside cells, including many involved in cancer. Studies suggest that turning off Myc causes cancer cells to self-destruct in a process called apoptosis.
“The notion that targeting Myc will cure cancer has been around for a long time,” said cancer biologist Hans-Guido Wendel of Sloan-Kettering. “Blocking production of Myc is an interesting line of investigation. I think there’s promise in that.”
Targeting Myc, however, has been a backwater of drug development. “Personalized medicine” that targets a patient’s specific cancer-causing mutation attracts the lion’s share of research dollars.
“The biggest obstacle” to a true war against cancer, Watson wrote, may be “the inherently conservative nature of today’s cancer research establishments.” As long as that’s so, “curing cancer will always be 10 or 20 years away.”
(Reporting by Sharon Begley; Editing by Jilian Mincer and Peter Cooney)
Cancer survivors: Reconnecting with loved ones after treatment
By Mayo Clinic staff
Your friends and family love you and are worried about you — but they sometimes have strange ways of showing it. Some people withdraw and avoid talking to you. Others smother you and treat you like a child.
Many cancer survivors find that one barrier to a smooth transition out of cancer treatment is the reaction they get from friends and family. One way for cancer survivors to prepare for relationship difficulties is to expect these problems and plan accordingly.
Common relationship issues for cancer survivors
Chances are you’ve noticed that some of your relationships have felt strained since you ended your cancer treatment. You’ve probably felt alone and sad as you’ve seen people turn away from you or otherwise treat you differently from how they had before. Navigating relationships is a challenge for cancer survivors transitioning to life after treatment.
You may recognize some of these common scenarios:
Changing responsibilities. During treatment, you might not have been able to handle all the household duties you had performed before your cancer diagnosis. For instance, maybe you were in charge of grocery shopping and cooking dinner. If cancer treatment tired you out and you were unable to continue those tasks, your partner or another family member might have filled in for you. Now that your cancer treatment is over, that person might be expecting you to resume those responsibilities — but you might not feel up to it yet. This can be frustrating for your family member, and you might feel pressured to do more than you can handle.
Changing roles. If you were a take-charge kind of person before cancer, you may find that during treatment your partner had to take over that role. Deciding when and how to switch back can be confusing and awkward.
Withdrawing from you. You may find that some friends and family members are avoiding you. It could be subtle or overt, such as when someone stops returning your phone calls. Either way, it hurts. People withdraw for a number of reasons. The person might not know what to say or is worried about saying the wrong thing. He or she might not know how to offer you support. Others don’t know how to react.
Giving you too much attention. Rather than feeling lonely, you might find yourself being smothered with good intentions. Friends or family might baby you and insist on doing things for you when no assistance is needed. They love you and want to help, but in fact they’re too helpful.
Being nosy. Some people ask a lot of questions — perhaps more than you’re comfortable answering.
Confusing expectations. If your recovery isn’t going as well as you’d hoped, you might be frustrated. You might expect everything to go back to normal right away, but that isn’t happening. Try not to take your frustrations out on the people around you. If you do, you could push them away.
Whether you encounter problems with your relationships often depends on the strength of the relationships beforehand. Relationships that were already strained tend to continue that way after cancer, sometimes completely falling apart. Strong relationships can become even stronger through the cancer experience.
Before feelings of loneliness and isolation get you down, remember that you can take steps to nurture relationships with friends and family. The first step is to acknowledge that all of these people care about you, and they each have their own way of reacting to your cancer.
Tips for repairing relationships include:
Start the conversation. Some people might want to ask how you’re feeling, but they don’t know what to say. Or maybe they think they’ll upset you. Start the conversation yourself. Let people know that you welcome their questions — or that you don’t wish to talk about your cancer at that time.
Accept help. Friends and family are going to ask you if there’s anything they can do to help. Plan ahead and come up with ways for people to give you some assistance, whether it’s helping around the house or just being there for you when you need to talk. Friends and family feel good when they can help.
Let others know what to expect of you. Be honest about what you can do and what you can’t. If you aren’t ready to assume the responsibilities you had around the house before your cancer diagnosis, don’t feel pressured to take up those duties too soon. But tell your family what to expect so that they aren’t left wondering. When you’re ready to take up your prior duties, let your family know that these tasks can help you feel more normal and aid in your recovery.
Keep the friendships that matter. Some people may withdraw from you, and you’ll have to let them go. Try not to expend a lot of emotional energy trying to patch up relationships that may not have been strong to begin with. Invest your time and energy in the friends who are closest to you.
Plan what you’ll say. You’ll get questions about your cancer and your treatment. Decide how you’ll answer these questions — especially if someone asks questions you don’t feel comfortable answering. In some situations you might let the person know that you don’t feel comfortable answering those questions. Other times you might avoid answering an uncomfortable question by changing the subject or redirecting the conversation.
Be patient with others. If you find yourself becoming frustrated, remember that the people around you have good intentions. They may not know the right things to say or do, so their words and actions may seem inappropriate or critical. That awkwardness may come from unfamiliarity with the situation. With time and patience, things may improve.
Stay involved when you can. Some friends or family might not invite you to do things because they assume you aren’t yet ready for social activities. Let these people know when you want to be included — or ask someone else to relay your message.
Seek out support groups. You’ll have times when you feel that people who haven’t had cancer can’t understand what you’re going through. Discuss your feelings with other cancer survivors, whether in a support group in your community or online. Support groups are also available for cancer survivors’ friends and family. Suggest these to the people closest to you.
Get professional help. Ask your doctor for a referral to a counselor or therapist for more help. He or she may have ideas on ways to better communicate with your friends and family.
It’s entirely possible that everyone in your family and in your circle of friends will be supportive throughout your recovery. But chances are that you will run into a few relationship obstacles. Think ahead about how you’ll deal with potential problems.
Living With Cancer: Dancing With N.E.D.
By SUSAN GUBAR
The vocalist begins her song with people shocked by a diagnosis they cannot accept, women not yet ready to admit they have cancer.
Starts with denial, there must be some mistake; Check the name, check the lab, double-check the date.
While electric guitars and percussion join in, the lyrics of the song, “Third-Person Reality,” go on to describe turbulent anger, tension and fear that can only be eased by acceptance.
Measure success one day at a time Together we’ll get to a better place If you place your hand in mine.
The symbol of women with cervical, endometrial, ovarian, peritoneal, tubal, vaginal, and vulvar cancers— a teal ribbon—often goes unrecognized, but these patients do have their own rock band. Through the driving rhythms of folk-rock, the band members of N.E.D. accompany a refrain made especially meaningful by the fact that they are all surgeons who treat patients with gynecological cancers. The group started as a cover band to entertain doctors at a 2008 meeting of the Society of Gynecological Oncologists. Since then they have taken on a mission “to break through the silence of women’s gynecological cancer.” In the process, they have produced two albums to raise awareness and money for research.
The band’s name strikes a special chord with anyone who has had cancer. The acronym, N.E.D., stands for that rapturous moment when patients are told that there is “no evidence of disease.”
The band’s debut year, 2008, happens to be the year I was diagnosed with ovarian cancer, and I find myself learning from N.E.D.’s Web site about the umbrella term — “gynecologic cancers” — within which my disease resides. The American Cancer Society estimates that about 83,000 women are diagnosed each year with cancers “below the belt,” and approximately 28,000 die from them. Yet with the notable exception of the brilliant comedienne Gilda Radner, who had ovarian cancer, no celebrity has emerged to represent the plight of these patients.
That fact may illustrate how stigmatized these diseases remain. Do women with gynecological cancers still find it difficult to overcome modesty about difficult-to-discuss body parts, even in this current age when such body parts seem weirdly chatty? Notwithstanding Eve Ensler’s historic “Vagina Monologues” and Naomi Wolf’s narcissistic “Vagina,” I suspect that quite a few women do not want to publicize their relationship with their genitals — especially when sexual and reproductive organs are imperiled by disease. Who can blame them and more power to them, I think.
After all, the title of the song “Third-Person Reality” suggests that people with cancer often feel so traumatized that they lose the ability to experience or express their sense of themselves. Alas, they may have morphed from first-person individuals into third-person patients, waiting interminably for this test or undergoing that procedure or paying for another script for yet another drug — even if, as in my lucky case, a caring oncologist offers a helping hand.
There are and have been prominent women whose recognition could call attention to gynecological cancers. Think of the award-winning actress Carol Channing or Miss America of 1945, Bess Myerson. Other exceptional people were swirled into the swing and sway of N.E.D. for only a round or two. The British biophysicist Rosalind Franklin lived long enough to illuminate the molecular structure of DNA, but her death made her ineligible for the Nobel Prize accorded Watson and Crick (who barely acknowledged her contribution). President Obama’s mother, Ann Dunham, raised two remarkable children while completing a Ph.D. in anthropology and helping to establish micro-industries in Indonesia before she
was misdiagnosed with one gynecological disease and died of another. That Dr. Franklin was 37 years old and Ms. Dunham 52 reminds us that such cancers do not single out aged women.
A few weeks ago I received a heart-breaking e-mail from a mother whose daughter, Taylor Steele, died of ovarian cancer at 17. The Web site of the nonprofit foundation Strong as Steele informs me that Taylor Steele loved to dance, but she did not get much time with N.E.D. after she was diagnosed at 12.
And then there are people like me who are diagnosed later in life but can’t fill out an N.E.D. dance card because, unfortunately, we still have E.D. (evidence of disease). That said, I am here to add that it is possible, if only intermittently, to hum along with E.D., which has its own sometimes somber but sometimes revitalizing rhythms.
The physician-musicians of N.E.D named their second CD “Six Degrees” for their six medical degrees, but also for the six degrees of separation between patients with gynecological diseases and everyone else. The title reminds me that every six minutes an American girl or woman discovers that she has a gynecological cancer. Let us hope that future research will develop new detection tools and improved treatments, giving each one a longer time to twist and shout with N.E.D.
HER2-positive breast cancer: What is it?
Sandhya Pruthi, M.D.
HER2-positive breast cancer is a breast cancer that tests positive for a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells. In about 1 of every 5 breast cancers, the cancer cells make an excess of HER2 due to a gene mutation. This gene mutation and the elevated levels of HER2 that it causes can occur in many types of cancer — not only breast cancer. This is a gene mutation that occurs only in the cancer cells and is not a type of mutation that you can inherit from a parent.
HER2-positive breast cancers tend to be more aggressive than other types of breast cancer. They’re also less responsive to hormone treatment. However, treatments that specifically target HER2 are very effective. They include:
Trastuzumab (Herceptin). Trastuzumab, which specifically targets HER2, kills these cancer cells and decreases the risk of recurrence. Trastuzumab is often used with chemotherapy. But it may also be used alone or in combination with hormone-blocking medications, such as an aromatase inhibitor or tamoxifen. Trastuzumab is usually well tolerated, but it does have some potential side effects, such as congestive heart failure and allergic reaction.
Lapatinib (Tykerb). Like trastuzumab, lapatinib is a HER2-specific drug. Lapatinib may be effective for HER2-positive breast cancer that doesn’t respond to trastuzumab. Lapatinib is used in combination with the chemotherapy drug capecitabine (Xeloda) and the aromatase inhibitor letrozole (Femara). Lapatinib is also being studied in combination with trastuzumab. Common side effects include rash, loose stools and the potential risk of congestive heart failure.
In addition, there are several new medications being developed that also target HER2 and are being tested in clinical trials.
Standard chemotherapy agents such as doxorubicin (Adriamycin) also can be effective in treating HER2-positive breast cancers, although these drugs don’t specifically target the HER2 protein.
Routine testing for HER2 is recommended for most women diagnosed with invasive breast cancer because the results may affect treatment recommendations and decisions. HER2 testing is not done routinely for ductal carcinoma in situ but may be performed as part of a clinical trial. Whenever breast cancer recurs or spreads, the cancer cells should be retested for HER2 as well as for hormone receptor status, as these can change from the original cancer in up to 20 to 30 percent of cases.