Breast Cancer / Breast Cancer - Abstracts

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.