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Is screening for breast cancer with mammography justifiable?
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.
Efficacy of screening mammography. A meta-analysis.
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.
Effect on breast cancer mortality of biennial mammographic screening of women under age 50.
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.
Swedish study questions mammography screening programmes. News.
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.
Mammographic screening does not reduce breast cancer mortality. Swedish.
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.
Neglected aspects of false positive findings of mammography in breast cancer screening: analysis of false positive cases from the Stockholm trial.
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.
Breast screening: the case for physical examination without mammography.
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."
"Benign" tumors and "early detection" in mammography-screened patients of a natural cohort with breast cancer.
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.
TAMOXIFEN FOR BREAST CANCER PREVENTION
Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. Italian Tamoxifen Prevention Study.
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.
Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial.
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.
Effects of tamoxifen on uterus and ovaries of postmenopausal women in a randomised breast cancer prevention trial.
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.
Prevention trials with tamoxifen may be delayed in US. News
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.
Side effects of tamoxifen are distressing and common. Letter.
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.
The effect of physician recommendation on enrollment in the Breast Cancer Chemoprevention Trial.
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.
Breast cancer--a challenge to the contemporary paradigm.
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.
Survival of women with metastatic breast cancer at Yale from 1920 to 1980.
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.
No relevant influence on overall survival time in patients with metastatic breast cancer undergoing combination chemotherapy.
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.
Problems associated with randomized controlled clinical trials in 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.
Do patients with advanced breast cancer benefit from chemotherapy?
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.
Intensive diagnostic follow-up after treatment of primary breast cancer. A randomized trial. National Research Council Project on Breast Cancer follow-up.
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.
Impact of follow-up testing on survival and health-related quality of life in breast cancer patients.
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.
Effects of radiotherapy and surgery in early breast cancer. An overview of the randomized trials.
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.
Ten-year results of a comparison of conservation with mastectomy in the treatment of stage I and II breast cancer.
Jacobson JA, et al.
N Engl J Med 1995 Apr 6;332(14):907-11.The results of this study show that women with early breast cancer (stage I and stage II) who underwent surgical removal of the entire breast gland (mastectomy) had no better relapse-free and overall 10-year survival than women who underwent conservative breast surgery (lumpectomy) followed by radiation.
Morbidity following sentinel lymph node biopsy versus axillary lymph node dissection for patients with breast carcinoma.
Schrenk P, Rieger R, Shamiyeh A, Wayand W.
Cancer 2000 Feb 1;88(3):608-14.The results of this study show that selective removal of the first few underarm lymph nodes that receive tumor drainage (sentinel lymph nodes) during breast cancer staging is associated with significant fewer side effects than more extensive lymph node removal. Traditionally up to 26 underarm lymph nodes are removed to determine whether the cancer has spread. This procedure is associated with considerable complications such as edema of the arm, pain, nerve damage, impaired mobility and shoulder stiffness. Post-operative morbidity was assessed in 35 breast cancer patients who underwent traditional lymph node removal (with dissection of 10-26 nodes), and in 35 breast cancer patients who underwent sentinel lymph node removal (with dissection of 1-4 nodes). In the months after surgery, numbness, arm edema and pain occurred in 24, 19, and 16 of the 35 women who underwent extensive lymph nodes removal, respectively. On the other hand, none of the women with sentinel lymph node removal had numbness or arm edema, and only 2 had minor pain. These data indicate that removal of sentinel underarm lymph nodes is associated with negligible side effects compared to complete lymph node resection, and should therefore be incorporate in current treatment practices.
Randomized trial of high-dose chemotherapy and blood cell autografts for high-risk primary breast carcinoma.
Hortobagyi GN, et al.
J Natl Cancer Inst 2000 Feb 2;92(3):225-33.The results of this study show that cancer treatment with high dose chemotherapy and autologous stem cell transplant in women with breast cancer is associated with increased morbidity and mortality compared to standard-dose chemotherapy. The treatment consists of removing stem cells from patients' bone marrow and blood, delivering high doses chemotherapy, and re-injecting stem cells back to the patients. In this study, 78 women were treated with standard chemotherapy for breast cancer. Subsequently, 39 of them were randomized to receive no further treatment, and 39 to undergo two cycles of high-dose chemotherapy with stem cell transplant. Survival rates at 3 years were 62% in the group who received standard-dose chemotherapy only, and 48% in those who received standard treatment with high-dose chemotherapy. Complications of treatment (including one death from septic shock) were significantly more serious and more frequent in women undergoing high-dose chemotherapy.
Conventional-Dose Chemotherapy Compared with High-Dose Chemotherapy plus Autologous Hematopoietic Stem-Cell Transplantation for Metastatic Breast Cancer.
Stadtmauer, EA. et al.
N Engl J Med 2000;342.The results of this study show that high-dose chemotherapy with autologous bone marrow stem -cell transplant does not improve survival, compared to conventional chemotherapy, in patients with advanced breast cancer. The study was conducted on 199 women aged 18-60 years, who were randomized to receive, after conventional chemotherapy, either high-dose chemotherapy followed by infusion of patient' own stem cells, or conventional chemo. No significant differences in survival were observed between the two groups during a 3-year follow-up period. Overall three-year survival rates were 32% in the high-dose chemotherapy group and 38% in the conventional dose chemotherapy group.
High-Dose Chemotherapy plus Autologous Bone Marrow Transplantation for Metastatic Breast Cancer. Editorial.
Lippman, M.E.
N Engl J Med 2000;342.This letter highlights that in spite of the results of several phase II trials indicating impressive survival benefits in patients undergoing high-dose chemotherapy compared to historical controls, rigorous analysis of these trials revealed severe bias involving patients' selection processes, and the studies' conclusions could not be subsequently validated. In addition it was demonstrated that comparison with historical controls added further bias that affected the interpretation of the studies' outcomes. The author concludes that, based on the available evidence, use of high-dose chemotherapy in women with metastatic breast cancer is ineffective, and that new, more promising treatments should be pursued.
High-dose chemotherapy for high-risk primary breast cancer: an on-site review of the Bezwoda study.
Weiss,RB. et al.
Lancet 2000; 355: 999 - 1003.This article reports on the results of an on-site review of the clinical records of patients who participated to two studies, lead by a South African researcher, which demonstrated that high-dose chemotherapy with stem cell rescue prolongs life in women with breast cancer. The validity of this technique has been debated for a long time. While uncontrolled trials showed increased survival rates in women treated with high-dose chemotherapy, every randomized trial failed to confirm these preliminary results, with the exception of two studies by Bezwoda and colleagues, demonstrating a clear survival benefit. Bezwoda's trial showed that 5 years after treatment, 25% of women who had received high-dose chemotherapy and bone marrow transplantation had relapsed, compared to 66% of those who had received conventional chemotherapy treatment. When U.S. investigators visited South Africa to review these results, they found several inconsistencies between the records and the published data, and uncovered the death of at least seven extra women, in addition to the reported eight. In addition, no records of signed informed consent or approval for the investigational therapy were found. The results of the study were discounted, and Bezwoda admitted scientific misconduct.
Polychemotherapy for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists' Collaborative Group.
Lancet 1998 Sep 19;352(9132):930-42.This study presents an overview of the results of 47 clinical trials conducted on approximately 18,000 women, investigating the effects of polychemotherapy on breast cancer outcome. It was shown that several months of multiple agent chemotherapy produced a 7%-10% increase in overall 10-year survival in women under the age of 50 with stage I or stage II breast cancer, and a 2%-3% increase in overall 10-year survival in women aged 50-69. Chemotherapy delivered for longer than 3-6 months was not associated with further improvements in outcome. The authors conclude that the benefits of treatment must be weighted against the adverse effects associated with therapy.
Discordance between physicians' estimations and breast cancer patients' self-assessment of side-effects of chemotherapy: an issue for quality of care.
Macquart-Moulin G; et al.
Br J Cancer, 76(12):1640-5 1997.This study shows that women with breast cancer receiving chemotherapy experience significant more side effects that their physicians are aware of. For example, physicians reported that hair loss and nausea occurred in 27% and 38% of treatment cycles, respectively, while patients reported these symptoms in 80% and 73% of cycles. The incidence of treatment-related adverse effects was high, and patients reported that hot flushes, stomach pain and pain in the articulations or muscles occurred in approximately half of the cycles, with symptoms lasting 1 week or longer. Hot flushes, vomiting and stomach pain were particularly distressing. This study shows that physicians have limited awareness of the prevalence of side effects in patients treated with chemotherapy. This information is important in order to deliver proper quality of care.
Long-term cardiac morbidity and mortality in a randomized trial of pre- and postoperative radiation therapy versus surgery alone in primary breast cancer.
Gyenes G, Rutqvist LE, Liedberg A, Fornander T.
Radiother Oncol 1998 Aug;48(2):185-90.The results of this study show that radiation therapy given before or after surgery in women with breast cancer is associated with a two-fold increased risk of death from cardiovascular disease, compared to surgery alone. The authors note that the increase in cardiovascular death is especially due to an increase in death from ischemic heart disease and not from myocardial infarction.
Postoperative radiotherapy and late mortality: evidence from the Cancer Research Campaign trial for early breast cancer.
Haybittle JL; Brinkley D; Houghton J; A'Hern RP; Baum M.
BMJ, 298(6688):1611-4 1989 Jun 17.The results of this study show that women with early (stage 1 or stage 2) breast cancer who underwent surgery followed by radiation therapy had higher overall mortality rates than those who after surgery received no further treatment. While radiation therapy was associated with a small decrease in breast cancer mortality (3% decrease), it was also linked to a 37% increase in mortality from other causes. In particular, radiation therapy was associated with a 65% increased risk of death from cardiac disease and with an over twofold increased risk of death from other cancers.
Mortality from myocardial infarction after adjuvant radiotherapy for breast cancer in the surveillance, epidemiology, and end-results cancer registries.
Paszat LF; Mackillop WJ; Groome PA; Boyd C; Schulze K; Holowaty E.
J Clin Oncol, 16(8):2625-31 1998 Aug.The results of this study show that women younger than 60 years of age with left-sided breast cancer who received adjuvant radiation therapy had a two-fold increased risk of dying from myocardial infarction, compared to women with breast cancer who had been irradiated in the right side of the chest.
A randomized trial of chemotherapy (L-PAM vs CMF) and irradiation for node positive breast cancer. Eleven year follow-up of a Piedmont Oncology Association trial.
Muss HB, et al.
Breast Cancer Res Treat, 19(2):77-84 1991 Oct.The results of this study, conducted over an 11-year period, show that the addition of radiation therapy to chemotherapy in women with locally advanced breast cancer is not associated with improved relapse-free or overall survival.
Adjuvant chemotherapy plus tamoxifen compared with tamoxifen alone for postmenopausal breast cancer: meta-analysis of quality-adjusted survival.
Gelber RD, et al.
Lancet 1996 Apr 20;347(9008):1066-71.The results of this meta-analysis show that treatment with chemotherapy and tamoxifen is no better than treatment with tamoxifen alone in improving survival or quality of life in postmenopausal women with node-positive breast cancer. A review of the results of nine trials involving almost 4,000 women showed that those who received chemotherapy in addition to tamoxifen had, over a 7-year period, a statistically non-significant average gain of 2 months in overall survival compared to those who received tamoxifen only. To achieve this statistically non-significant gain, patients had to receive chemotherapy for a period of 2-24 months. The authors concluded that chemotherapy did not add more quality-adjusted survival time to postmenopausal patients with node-positive breast cancer.
Six-year results of the Eastern Cooperative Oncology Group trial of observation versus CMFP in postmenopausal patients with node-positive breast cancer.
Taylor SG 4th; et al.
J Clin Oncol, 7(7):879-89 1989 Jul.The results of this study, conducted on 265 postmenopausal women with breast cancer and positive underarm lymph nodes, show that after 6 years of follow-up, mortality rates in women who underwent surgery followed by chemotherapy or by chemotherapy plus tamoxifen were similar to those of women who received surgery alone.
Incidence of new primary cancers after adjuvant tamoxifen therapy and radiotherapy for early breast cancer.
Andersson M, Storm HH, Mouridsen HT.
J Natl Cancer Inst 1991 Jul 17;83(14):1013-7.The results of this study show that the addition of tamoxifen to radiation therapy for the prevention of breast cancer recurrence in postmenopausal women is not associated with improved survival, compared to radiation therapy alone. Over 1,700 women with breast cancer were randomized to receive after surgery, radiation therapy alone, or radiation therapy plus tamoxifen. Women were followed-up for an average of 8 years. There were no differences in the incidence of recurrent breast cancer in the two groups. Women receiving tamoxifen, however, had an over 3-fold increased risk of endometrial cancer, compared to those who received radiotherapy alone. In addition radiation treatment was found to be associated with an increased risk of leukemia, compared to the general population.
Risk of endometrial cancer after tamoxifen treatment of breast cancer.
van Leeuwen FE, et al.
Lancet 1994 Feb 19;343(8895):448-52.The results of this study show that women who use tamoxifen for more than 2 years have a 2.3-fold increased risk of uterine cancer, compared to nonusers.
Iatrogenic risks of endometrial carcinoma after treatment for breast cancer in a large French case-control study. Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC).
Mignotte H, et al.
Int J Cancer 1998 May 4;76(3):325-30.The results of this study show that use of tamoxifen is associated with a 5-fold increased risk of endometrial cancer, compared to nonuse. The risk increases with duration of treatment and with cumulative dose received. Endometrial cancer that develops in women treated with tamoxifen is more aggressive and is associated with a poorer prognosis than that arising in women not taking the drug. The study also found that women with breast cancer who underwent pelvic irradiation had an almost 8-fold increased risk of endometrial cancer, compared to those who were not irradiated.
Tamoxifen therapy for breast cancer and endometrial cancer risk.
Bernstein L, et al.
J Natl Cancer Inst 1999 Oct 6;91(19):1654-62.The results of this study show that breast cancer patients treated with tamoxifen have an overall 50% increased risk of endometrial cancer, compared to those who did not take the drug. The risk increased with duration of treatment, and women who took tamoxifen for 5 or more years had a 4-fold increased risk of endometrial cancer, compared to nonusers.
Discrepancy between ultrasonography and hysteroscopy and histology of endometrium in postmenopausal breast cancer patients using tamoxifen.
Mourits MJ, et al.
Gynecol Oncol 1999 Apr;73(1):21-6.The results of this study show that tamoxifen can induce specific changes in the uterus lining including enlargement of endometrial glands and endometrial polyps. Seven of 53 post-menopausal women taking tamoxifen developed endometrial polyps.
Endometrial cancer in polyps associated with tamoxifen use.
Ramondetta LM, Sherwood JB, Dunton CJ, Palazzo JP.
Am J Obstet Gynecol 1999 Feb;180(2 Pt 1):340-1.This article reports on the case of 5 women in which tamoxifen-induced endometrial polyps evolved in endometrial cancer.
Tamoxifen and risk of large bowel cancer in women with breast cancer.
Newcomb PA, Solomon C, White E.
Breast Cancer Res Treat 1999 Feb;53(3):271-7.The results of this study show that use of tamoxifen for 5 or more years is associated with a 50% increased risk of colorectal cancer, compared to nonuse.
Tamoxifen and risk of idiopathic venous thromboembolism.
Meier CR; Jick H.
Br J Clin Pharmacol, 45(6):608-12 1998 Jun.This study shows that women with a history of breast cancer currently taking tamoxifen have a 7-fold increased risk of developing deep venous thrombosis and pulmonary embolism, compared to women with a history of breast cancer who never used the drug or who have used it in the past.
Thromboembolic accidents in postmenopausal patients with adjuvant treatment by tamoxifen. Frequency, risk factors and prevention possibilities.
French.
Cutuli B, et al.
Bull Cancer 1995 Jan;82(1):51-6.The results of this study, conducted on 441 postmenopausal women with breast cancer, show that tamoxifen-associated thromboembolic complications occurred in 4.3% of them, and were fatal in two cases. The authors conclude that tamoxifen may be contraindicated in women at risk of deep venous thrombosis and pulmonary embolism.
The effect of adjuvant prednisone combined with CMF on patterns of relapse and occurrence of second malignancies in patients with breast cancer.
International (Ludwig) Breast Cancer Study Group.
Marini G; et al.
Ann Oncol, 7(3):245-50 1996 Mar.This study evaluated the effect of adding low dose prednisone to chemotherapy treatment in patients with breast cancer. The addition of the steroid prednisone allowed delivery of higher doses of chemotherapy (approximately 12% higher). Overall 13-year survival in patients receiving prednisone and higher dose of chemotherapy was 59%, while that of patients receiving chemotherapy alone was 65%. Treatment with predisone was associated with a two-fold increased risk of cancer metastasis to the skeleton, and with a three-fold increased risk of developing other types of cancer. The authors suggest further investigation of the effects of steroids, which are widely used to treat vomiting in patients receiving chemotherapy, on cancer development.
How American oncologists treat breast cancer: an assessment of the influence of clinical trials.
Belanger D; Moore M; Tannock I.
J Clin Oncol, 9(1):7-16 1991 Jan.The results of this study show that 80% of American physicians specialized in cancer treatment would prescribe adjuvant chemotherapy to premenopausal women with breast cancer without lymph node involvement and to postmenopausal women with lymph node involvement. However, the authors highlight, these recommendations go against the evidence gathered from clinical trials showing that chemotherapy in women with breast cancer and negative lymph nodes is not associated with improved survival, as it is not in post-menopausal women with breast cancer and positive nodes. These results demonstrate that treatment modalities are based more on personal beliefs than on scientific evidence.
Adjuvant cyclophosphamide, methotrexate, and fluorouracil in patients with axillary node-positive breast cancer: an update of the Guy's/Manchester trial.
Richards MA;et al.
J Clin Oncol, 8(12):2032-9 1990 Dec.The results of this study show that adjuvant chemotherapy in premenopausal women with node positive breast cancer is associated with prolonged relapse-free and overall survival. On the other hand, in postmenopausal women with node positive breast cancer, chemotherapy has no impact on disease-free and overall survival.
Toxicity of intra-arterial doxorubicin in locally advanced breast cancer.
Twelves CJ; Chaudary MA; Reidy J; Richards MA; Rubens RD.
Cancer Chemother Pharmacol, 25(6):459-62 1990.The results of this study show that women with locally advanced breast cancer who received injection of the chemotherapeutic drug doxorubicin in the artery supplying the affected breast, developed unacceptable high local toxicity that prompted interruption of the study.
Adjuvant chemo(immuno-)-therapy of primary breast cancer with adriamycin-cyclophosphamide (and levamisole)--six-year evaluation.
Schreml W; Lang M; Betzler M; Schlag P; Lohrmann HP; Heimpel H; Herfarth C.
Eur J Cancer Clin Oncol, 19(5):607-13 1983 May.The results of this study show that the addition of immunotherapy with levamisole to chemotherapy in patients with breast cancer and no signs of metastasis had no impact on disease-free and overall survival, while being associated with significant adverse effects, compared to chemotherapy alone.
Increased breast-cancer recurrence rate after adjuvant therapy with levamisole. A preliminary report.
Executive Committee of the Danish Breast Cancer Cooperative Group.
Lancet, 2(8199):824-7 1980 Oct 18.The results of this study show that immunotherapy with levamisole in addition to radiation therapy in women with node positive breast cancer is associated with higher tumor relapse and with a high incidence of adverse effects.
Second malignancies diagnosed in patients receiving chemotherapy at the Pennsylvania Hospital.
Lerner H; Marcovitz E; Schoenfeld D; Zaren H.
J Surg Oncol, 23(3):195-7 1983 Jul.The results of this study show that 35 of 2,020 cancer patients treated with chemotherapy developed a second, independent cancer in the 2 to 102 months following treatment. The majority of these secondary cancers occurred in individuals who received adjuvant chemotherapy for early stage breast and colorectal cancer, and who had much higher expected survival rates than patients with advanced disease. Although the link between chemotherapy and cancer development is hard to prove, at least one class of drugs, alkylating agents, has been demonstrated to be associated with the development of a form of leukemia that is resistant to treatment.
