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Breast Cancer / Breast Cancer - Abstracts
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Gotzsche PC, Olsen O.
Lancet 2000 Jan 8;355(9198):129-34.
The results of this study show that breast cancer screening with mammography does not reduce breast cancer mortality and is, therefore, unjustified. The authors came to this conclusion after reviewing the evidence presented by 8 clinical trials performed on half a million women, which represent the basis for the current recommendation to perform national breast cancer screening programs. They found that the randomization procedures used in 6 trials were biased in that the groups of women compared differed substantially in age and other risk factors. Furthermore, the exact number of women randomized in each group could not be determined in four of these trials. The only two trials that were properly randomized showed no decrease in breast cancer mortality from screening with mammography. The other six, inadequately randomized, trials showed a 25% reduction in breast cancer mortality. However, the authors highlight that together with a reduction in breast cancer mortality these trials also showed an increase in overall mortality in women receiving mammography screening, compared to those who did not. Therefore, if we accept these trials as unbiased, we must also accept that for every 1000 women screened biennially for 12 years, 1 breast cancer death will be avoided, but 6 more deaths from other causes will occur. If we accept these data as biased, than there is no evidence that breast cancer screening reduces breast cancer mortality.
Kerlikowske K, Grady D, Rubin SM, Sandrock C, Ernster VL.
JAMA 1995 Jan 11;273(2):149-54.
The authors of this study concluded, after performing a meta-analysis of 13 published trials, that breast cancer screening with mammography in women aged 40-49 is not associated with a reduction in breast cancer mortality.
Peer PG; Werre JM; Mravunac M; Hendriks JH; Holland R; Verbeek AL.
Int J Cancer, 60(6):808-11 1995 Mar 16.
The results of this study, conducted on a population of 13,500 women aged 35-49, show that breast cancer screening with mammography for 16 years did not result in any significant reduction in breast cancer mortality. Women participating in the screening program underwent mammographic examination every 2 years for 16 years. Their breast cancer mortality rates after 10 years were not different from those of a control group of women who did not undergo mammography.
Mayor, S.
BMJ 1999;318:621 ( 6 March ).
This article reports on the results of a Swedish study involving over 600,000 women, indicating that a national screening program with mammography conducted over a 10-year period had no effect in reducing breast cancer mortality. Breast cancer screening not only did not save lives, but also exposed a significant number of women to unnecessary interventions. Approximately 100,000 women received a false positive diagnosis. Of these, 16,000 underwent biopsy, and over 4,000 underwent surgery, including unnecessary mastectomy.
Sjonell G, Stahle L.
Lakartidningen 1999 Feb 24;96(8):904-5, 908-13.
The results of this study show that a program of breast cancer screening conducted during the period 1987-1996 had no significant effects in reducing breast cancer mortality when, according to clinical trials, it should have reduced it by 28%. The authors estimated the cost of saving one life through mammography screening at approximately $1.8 million.
Lidbrink,E. et al.
BMJ 1996;312:273-276 (3 February).
This study evaluated the extra procedures, diagnostic tests, and costs in women who received a false negative result during the Stockholm mammography screening trial. In the first and second round of the trial, 32,451 and 30,906 women, respectively, underwent breast cancer screening through mammography. Overall, 502 women received a false positive result, leading to 1,539 visits, 542 fine needle aspirations, 257 additional mammograms, and 118 biopsy, for an overall additional cost of pound sterling 334,000.
These costs substantially add to the pound sterling 1,267,000 cost of the screening and, although usually neglected, need to be taken in account when evaluating costs/benefit ratio of breast cancer screening programs.
Mittra I.
Lancet 1994 Feb 5;343(8893):342-4.
This article emphasizes that physical examination is considered as effective as mammography in reducing breast cancer mortality. While mammography can detect many small, non-infiltrating tumors it is possible that these tumors will never grow or pose a risk to a woman' life. It is not known if the time gained by early detection through mammography is associated with increased survival compared to detection through physical examination. The author concludes, "The question we should be asking is not how to refine mammographic screening but whether we need it at all."
Moody-Ayers SY, Wells CK, Feinstein AR.
Arch Intern Med 2000 Apr 24;160(8):1109-15.
The results of this study show that breast cancers detected by mammography screening are more benign than those detected by other methods, and are therefore associated with improved outcome, irrespective of treatment. The study was conducted on 233 women treated for breast cancer in 1988, of whom 42% had their cancer detected by mammography screening. After approximately 7 years of follow-up, 95% of women diagnosed by mammography were free from cancer, compared to 79% of those diagnosed by other methods. The improved outcome of cancers detected by mammography is partly due to fact that these tumors are detected at an early stage, and partly due to their more benign nature, as shown by the fact that, even among women with similar tumor stage, survival rates were distinctly improved in the group diagnosed by mammography, compared to the group diagnosed by other methods. These differences could not be explained by treatment, because all women, regardless of how their cancer was detected, were treated similarly. These data indicate that many of the cancers found during mammography screening are relatively benign and tend to progress very slowly, if at all.
If patients don't know that the majority of benign cancers will never cause them a problem, they will believe that screening saved their life, and the confidence in the screening program will be increased. This however, could translate in the flourishing of an industry not necessarily directed at patient's best interests.
Veronesi U, et al.
Lancet 1998 Jul 11;352(9122):93-7.
This study evaluated the effect of tamoxifen in preventing breast cancer. Since tamoxifen has been associated with increased risk of uterine cancer, only women who had their uterus removed were enrolled. Over 5,400 women participated. They were randomized to receive daily doses of either tamoxifen or placebo. After four years of follow-up, breast cancer rates in the two groups did not differ. Only a subgroup of women on hormone replacement therapy seemed to benefit from the anti-estrogenic effects of tamoxifen. Women taking tamoxifen had an increased risk of vascular events and high levels of blood triglycerides, compared to those taking placebo. These data indicate that tamoxifen is not effective in reducing breast cancer risk, and is associated with considerable side effects.
Powles T, et al.
Lancet 1998 Jul 11;352(9122):98-101.
This study, conducted on 2,471 healthy women, evaluated the effects of tamoxifen in preventing the occurrence of breast cancer. Women were randomized to receive daily doses of tamoxifen or placebo for up to 8 years. After a median 5 years of follow-up, the incidence of breast cancer did not differ in women taking placebo compared to those taking tamoxifen. The incidence of breast cancer was reduced only in a subgroup of women who were at increased risk of breast cancer from being on hormone replacement therapy.
Kedar RP, et al.
Lancet 1994 May 28;343(8909):1318-21.
The results of this study show that tamoxifen can induce potentially malignant changes in the uterus lining. Forty percent of healthy women who took tamoxifen to prevent breast cancer had histologic evidence of endometrial abnormalities compared to 10% of those who took placebo.
J Roberts.
BMJ 1994;308:1318 (21 May).
This article reports on the temporary interruption of a trial conducted on over 11,000 women that is testing whether tamoxifen reduces the incidence of breast cancer in women at risk of getting the disease. The trial was interrupted after it was discovered that the same researchers involved in the tamoxifen trial had falsified data in another trial of breast-conserving surgery. According to Cynthia Pearson of the National Women's Health Network no other preventive treatment carries as much risks as tamoxifen. Available data indicate that use of tamoxifen for 5 years is associated with a 2% risk of deep venous thrombosis or uterine cancer. This means that out of 8,000 women taking the drug, approximately 100 will suffer major illnesses and possibly 10-15 will die from the treatment.
Ray, A., Leonard, R. C F.
BMJ 1996;313:1484 (7 December).
Tamoxifen is an anti-estrogen drug used to prevent breast cancer in healthy women who are at higher than average risk of getting cancer or to prevent recurrence of disease in women who underwent surgical treatment for the disease. This letter emphasizes that treatment with tamoxifen is associated with substantial side effects. Hot flashes, weight gain, and vaginal discharge occurred respectively in 47%, 44%, and 28% of women taking tamoxifen compared to 16%, 18%, and 3% of control. These symptoms were described as distressing by the patients. The authors highlight the importance of informing patients adequately on the side effects associated with treatment.
Kinney AY; Richards C; Vernon SW; Vogel VG.
Prev Med, 27(5 Pt 1):713-9 1998 Sep-Oct.
The results of this study show that physician recommendation as to whether enroll or not in a clinical trial to prevent breast cancer is pivotal in determining the outcome of patients' decision of participating in the trial. In particular, women who were advised by their doctors to enroll in the trial were 13 times more likely to participate, compared to women who were advised by their doctor not to participate.
Baum M.
Acta Oncol, 35 Suppl 8():3-6 1996.
This article highlights that despite claims of great success achieved in breast cancer management, mortality rates from this disease have changed minimally with the advent of new therapies. The benefits derived from adjuvant systemic therapy achieved 20 years ago have been maintained and little further improvement has been demonstrated. The author also proposes that early surgery may shift the equilibrium of cancerous cell towards growth, and may therefore promote, rather than halt, cancer development.
Todd M; Shoag M; Cadman E.
J Clin Oncol, 1(6):406-8 1983 Jun.
The results of this study show that 5-year survival rates in patients with metastatic breast cancer increased from 5% in the 1920s to approximately 25% in the 1960s, and it remained 25% through the 1970s, despite the introduction of combination drug regimens. The authors conclude that current treatment modalities failed to improve survival rates of patients with metastatic breast cancer.
Petru E; Schm¨ahl D.
J Cancer Res Clin Oncol, 114(2):183-5 1988.
This study reviewed the results of clinical trials conducted between 1975 and 1986 evaluating the effects of chemotherapy on survival in women with metastatic breast cancer. It was shown that chemotherapy failed to improve overall survival in patients with late stage breast cancer.
Johnson AE.
J Eval Clin Pract, 4(2):119-26; discussion 127-30 1998 May.
This article questions the validity of using randomized controlled clinical trial to evaluate the effects of adjuvant therapy on breast cancer outcome. Patients entering clinical trials are selected on the basis of tumor staging, which is a poor indicator of tumor behavior. Metastases are the main determinant of tumor outcome, and they are undetectable until they reach about 10 mm in diameter, corresponding to approximately 3/4 of the tumor life span. It is impossible to determine at what point of development the tumor is, and therefore there is no basis to start a randomized trial. The author recommends alternative approaches to evaluate individual tumor responses to treatment.
Ramirez AJ, Towlson KE, Leaning MS, Richards MA, Rubens RD.
Br J Cancer 1998 Dec;78(11):1488-94.
This study was conducted on 155 women with advanced breast cancer receiving palliative chemotherapy (treatment aiming at improving patient quality of life or survival, but without intent of cure), who were asked to report their overall sense of well being before, during and after treatment (at about 24 weeks). Only 26% of women reported that they felt better after chemotherapy. Nineteen percent felt the same, and 22% felt worse. The remaining 33% of patients were treatment failures (they either died or stopped attending the hospital). These data indicate that three quarters of women with advanced stage breast cancer experience either no improvement in quality of life, or their quality of life worsens, when treated with palliative chemotherapy.
Rosselli Del Turco M, Palli D, Cariddi A, Ciatto S, Pacini P, Distante V.
JAMA 1994 May 25;271(20):1593-7.
The results of this study show that women with localized breast cancer who undergo intensive diagnostic follow-up after surgery, fare no better in terms of progression of disease and overall survival, than women who receive regular follow-up. The study was conducted on 1243 pre- and post-menopausal women who underwent surgery for breast cancer and had no signs of distant metastases, who were randomized to receive either normal clinical follow-up consisting of physical examination and mammography every year, or intensive follow-up with chest X-rays and bone scans performed every 6 months in addition to clinical follow-up. Intensive follow-up yielded to the detection of a greater number of tumor recurrences, with women becoming aware of cancer recurrence earlier in time, but early detection did not result in improved overall 5-year survival. On the basis of these results, the authors conclude that intensive diagnostic follow-up should not be routinely performed in women with breast cancer.
A later article entitled "Intensive vs clinical follow-up after treatment of primary breast cancer: 10-year update of a randomized trial. National Research Council Project on Breast Cancer Follow-up. Palli, D et al. JAMA. 1999 May 5;281(17):1586) reports on the results of a 10 year follow-up of both patients cohorts. Again, 10 year after primary diagnosis of breast cancer, women who had been followed up intensively showed no survival improvement compared to those with regular follow-up. Mortality rates were 34.8% in the cohort with intensive follow-up, and 31.5% in the cohort with clinical follow-up. The authors highlight that an increasingly bigger part of the health care budget costs is being invested in intensive follow-up screening of individuals with solid tumors. However, in the case of breast cancer there is no evidence indicating that diagnostic and laboratory tests other than mammography have a beneficial effect on survival.
A multicenter randomized controlled trial.
The GIVIO Investigators.
JAMA 1994 May 25;271(20):1587-92.
The results of this study show that intensive follow-up of women with early stage breast cancer does not result in improved survival or improved quality of life. The study was conducted on 1320 women with stage I, II, and III breast cancer who were randomized to undergo after surgery either intensive followed-up consisting of bone scans, chest X-rays, liver echography and laboratory tests performed at predetermined intervals during physicians visits, or regular follow-up consisting of physician visits with further testing prescribed only if clinically indicated. No differences in overall survival or quality of life were observed between the two groups during a 6-years follow-up period. These data indicate that intensive diagnostic measures do not improve the outcome of women with breast cancer and therefore should not be routinely performed in these patients.
Early Breast Cancer Trialists' Collaborative Group.
N Engl J Med, 333(22):1444-55 1995 Nov 30.
The results of this meta-analysis of 64 randomized trials involving over 28,000 women, show that those who received radiation therapy in addition to surgery had lower rates of local tumor recurrence but higher 10-year mortality rates, compared to those who received surgery alone. In particular radiotherapy was associated with a 6% reduced risk of death from breast cancer, but with a 24% increased risk of death from other causes. These results imply that, 10 years after treatment, there will be a few extra deaths among women who received radiation therapy compared to those who did not receive it. It was also shown that more extensive surgery is not associated with better 10-year survival rates compared to less extensive surgery, that mastectomy has no survival advantages over lumpectomy plus radiotherapy, and that mastectomy and removal of the under arm lymph nodes is no better than mastectomy with node conservation and radiation therapy. This study failed to find differences in overall 10-year survival in women receiving different local treatment for breast cancer.
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