BREAST SPECIFIC CHEMO
Journal of The American Medical Association,1979; 241(5): 489-494
On the Diagnosis and Treatment of Breast Cancer, By: Dr. Maurice S. Fox, Ph.D.
“…breast cancer mortality has remained unchanged for at least the past 40 years.”
Seminars in Oncology, New agents and new medical treatments for advanced breast cancer. 14:1 1987 Mar pg 34-64. By: Henderson IC, Hayes DF, Come S, Harris JR, Canellos G. “Most retrospective studies have failed to show that the survival of patients with advanced breast cancer has changed very much over the past 20-30 years.”
Annals of Oncology, 2002, Volume 13, Issue 2, Pages: 197-207, Second and subsequent lines of chemotherapy for metastatic breast cancer: what did we learn in the last two decades? By: F. Cardoso, A. Di Leo, C. Lohrisch, C. Bernard, F. Ferreira and M. J. Piccart.
“Despite almost 30 years of clinical cancer research, the true impact of second and subsequent lines of chemotherapy on the outcome of metastatic breast cancer patients, especially on the duration of survival, is still unknown.”
“The breast cancer mortality rate has remained stable for several decades…”
“Chemotherapy was introduced as an anticancer therapy in the 1950s and combination chemotherapy started to be routinely used in the 1970s. Surprisingly, more than half a century later, its true impact on MBC patients’ survival is still a matter of debate. There is a general consensus that the role of cytotoxic therapy in prolonging survival in MBC patients is modest, and that the efficacy of second and subsequent lines of chemotherapy, also called ‘salvage’ therapy regimens, is uniformly poor.” (See 1-4 below)
1. Muss HB, Case D, Richards F et al. Interrupted versus continuous chemotherapy in patients with metastatic breast cancer. N Engl J Med 1991; 325: 1342–1348.
2. Nabholtz JM, Senn HJ, Bezwoda WR et al. Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with MBC progressing despite previous anthracycline containing chemotherapy. J Clin Oncol 1999; 17: 1413–1424.
3. Sjostrom J, Blomqvist C, Mouridsen H et al. Docetaxel compared with sequential methotrexate and 5-fluorouracil in patients with advanced breast cancer after anthracycline failure: a randomised phase III study with crossover on progression by the Scandinavian Breast Group. Eur J Cancer 1999; 35: 1194–1201.
4. Fossati R, Confalonieri C, Torri V et al. Cytotoxic and hormonal treatment for metastatic breast cancer: a systematic review of published randomized trials involving 31,510 women. J Clin Oncol 1998; 16: 3439–3460.
“Since treatment for MBC [Metastatic Breast Cancer] is not curative, QOL [Quality of Life] is an important issue to consider when selecting a treatment regimen…”
Der Spiegel, 2004, April 10, pages 160 -162
Poison-without benefit, By: Jörg Von Blech
“Survival rates have not improved over the past decades. Today’s patients die just as fast of their cancer as their fellow sufferers did 25 years ago.”
The Lancet, 1980 Mar 15;1(8168 Pt 1):580-2, Failure of chemotherapy to prolong survival in a group of patients with metastatic breast cancer. By: Powles et al. “Overall survival of patients with primary breast cancer has not improved in the past ten years, despite increasing use of multiple-drug chemotherapy for treatment of metastases. Furthermore, there has been no improvement in survival from first metastasis, and survival may even have been shortened in some patients given chemotherapy. …. Actuarial survival analysis … reveals no prolongation in overall survival, despite the increased use of multiple-drug chemotherapy for metastatic disease. The survival of the 78 patients who received chemotherapy from first detection of metastases (including single-agent chemotherapy) was no better than that of the 80 who did not receive chemotherapy. There was also no improvement in survival for those who received multiple-drug chemotherapy (66 patients)…. The fact that regressions of breast cancer had no influence on overall survival must reflect the inadequacy of present-day chemotherapy.”
Breast Cancer Research and Treatment,1981, Volume 1, Issue 4, pp 357-363
Effect of chemotherapy on survival in metastatic breast cancer, By: Alexander H. G. Paterson M.D., et al. “…chemotherapy may be improving short-term survival in some patients, but is making no major impact on long-term survival.”
Cancer, 1986 Feb 1;57(3):567-70. Does more intense palliative treatment improve overall survival in metastatic breast cancer patients? By: Patel et al.
A retrospective review of 483 breast cancer patients treated between 1942 and 1975. It was found that despite a changing trend in therapy away from radiation and additive hormones towards chemotherapy and ablative hormones there was no increase in survival time from first diagnosis, or metastatic survival time, (from appearance of first metastasis).
Journal of Cancer Research and Clinical Oncology, No relevant influence on overall survival time in patients with metastatic breast cancer undergoing combination chemotherapy, April 1988, Volume 114, Issue 2, pp 183-185, By: E. Petru, D. Schmähl
9350 Women were studied over an 11 year period. There were 40 different 1st line drug combinations used and 50 different 2nd line drug combinations.
“Our special aim was to evaluate combination chemotherapy and its influence on overall survival in late stage breast cancer patients. No significant improvement in overall survival times was found in the selected group of patients who were treated with intense palliative chemotherapy.”
“We think that from the ethical point of view it seems problematic to apply aggressive chemotherapy programs to patients with metastatic disease, since no significant therapeutic effect in terms of prolongation of life-span can be assumed.”
British Journal of Cancer, Does chemotherapy improve survival in advanced breast cancer? A statistical review, 1988; 57: pages 615–618. By: A’Hern, Ebbs, & Baum.
“Treatment attempts to prolong survival but trials rarely demonstrate a statistically significant survival advantage: it has been argued that chemotherapy does not prolong survival.”
South African Medical Journal, 2011, Vol. 101, No. 11
Genetic profiling in breast cancer, By: Edge & Panieri
“Of women with early breast cancer who receive chemotherapy 70 – 80% do not benefit from the treatment…”
Journal of Clinical Oncology, A prospective randomized trial comparing epirubicin monochemotherapy to two fluorouracil, cyclophosphamide, and epirubicin regimens differing in epirubicin dose in advanced breast cancer patients. vol.9, No.2, 1991, pp.: 305-312, By: The French Epirubicin Study Group.
“The two trials gave comparable results; in both studies, the response rates were not different for the two regimens, and no differences were observed in duration of response, time to progression, and survival.”
Cancer, A randomized trial of two dosage schedules of mitomycin C in advanced breast carcinoma,1992 Jan 15;Vol 69, No.2, pages:476-81. By: Walters, Frye, Buzdar, Holmes & Hortobagyi. 67 breast cancer patients were included in this study.
“Unfortunately, although there were fewer toxic effects, disease progression did not allow the administration of more therapy; therefore, remission duration, time to progression, and survival rate were not prolonged significantly.” (Too many patients died)
Journal of Clinical Oncology, A decade of breast cancer clinical investigation: results as reported in the Program/ Proceedings of the American Society of Clinical Oncology. September 1994 vol. 12 no. 9 pages: 1789-1795, By: R T Chlebowski and L M Lillington
“These results suggest that a critical process evaluation of current policy and procedures involved in directing breast cancer research is warranted, especially for strategies in advanced disease. . . trials of advanced breast cancer therapy have remained relatively small and have consistently failed to support study hypotheses or identify successful new management approaches as defined by a significant impact on patient survival. . . Is it prudent, or even ethical, to continue to conduct clinical trials in advanced breast cancer populations based on demonstrably unreasonable assumptions of the anticipated magnitude of benefit?”
British Journal of Cancer, High-dose chemotherapy of metastatic breast cancer: the end of the beginning? 1997; 75(4): 467–469. By: J. Crown “The survival impact of chemotherapy in metastatic breast cancer is limited, and the disease remains essentially incurable.”
Annals of Oncology, 2012, no. 23; pages 547–555. Cytotoxic drugs for patients with breast cancer in the era of targeted treatment: back to the future? By: J. T. Ribeiro et al.
Conclusion: “Toxicity and chemotherapy resistance are still major limitations in the treatment of patients with MBC (Metastatic Breast Cancer). Further research into new cytotoxic compounds is needed in order to maximise benefit, whilst minimising toxicity.” It concludes with, “The main issue is still toxicity, as most of the compounds tested have displayed, at best, a distinct adverse event profile.”
Journal of the American Medical Association, September 4, 1991, Vol 266, No. 9.
The Evolution of Breast Cancer Treatment, By: Dr. Edward F. Scanlon, M.D., Former president of the American Cancer Society and professor emeritus of surgery at Northwestern University Medical Center. “over a period of 100 years, breast cancer treatment has evolved from no treatment to radical treatment and back again to more conservative management, without having affected mortality.”
The Oncologist, 2005;10(suppl 3):20–29 By: Joyce O’Shaughnessy
Baylor-Sammons Cancer Center, Dallas, Texas, USA
Extending Survival with Chemotherapy in Metastatic Breast Cancer
Metastatic breast cancer (MBC) remains essentially incurable…In the treatment of MBC, there is an underlying assumption that improvements in overall response rates would translate into long-term survival benefits. While there is indirect evidence to support a relationship between response and overall survival, few randomized trials have provided direct evidence.
The assessment of the *true survival benefits from chemotherapy in MBC can be difficult, given the potential for confounding issues, such as the impact of subsequent therapies.
*”True survival benefits”… Is the patient alive and healthy?
Cancer Treatment Reviews, Systematic reviews of chemotherapy and endocrine therapy in metastatic breast cancer. (2000), 26 (3), pp. 151-168. By: Stockler M., Wilcken N.R.C., Ghersi D., Simes R.J. “Metastatic breast cancer is incurable….” as well as, “There is little evidence-based consenus on when to use which treatments, in what combination and for how long.” [Since you say incurable, why would you put people through the hell of chemotherapy?]
Journal of Clinical Oncology, 2003; vol. 21 no. 6: p 959-962
Are anthracycline-taxane regimens the new standard of care in the treatment of metastatic breast cancer? By: Valero and Hortobagyi
This editorial by Valero and Hortobagyi reviews all of the large, prospective, randomized trials published comparing the newer, taxane-based chemotherapy regimens. These authors conclude that none of these regimens have increased either complete response rates or overall survival, with median survivals remaining at 2 years or less, or precisely the same results which were being obtained 30 years ago.
British Medical Journal, May 4, 2002; 324(7345): 1088–1092.
Presumed benefit: lessons from the American experience with marrow transplantation for breast cancer. By: H Gilbert Welch, professor of medicine and Juliana Mogielnicki, research assistant. “Few stories in medicine are as sobering as the American experience with autologous bone marrow transplantation (ABMT) for treating breast cancer. It is a story of young women dying from aggressive disease, well meaning physicians trying to be equally aggressive in treating it, and lawyers arguing that insurers should pay the bill. It is also a story of professional interests, weak research, financial gain, politics, and fraud. Because of its potential relevance to complex cancer therapies currently in development (such as gene therapy) we recount here the story and its lessons.”
European Journal of Cancer, 2004 Mar;40(4):536-42.
Multicentre, phase II study evaluating capecitabine monotherapy in patients with anthracycline- and taxane-pretreated metastatic breast cancer.
Fumoleau P1, Largillier R, Clippe C, Dièras V, Orfeuvre H, Lesimple T, Culine S, Audhuy B, Serin D, Curé H, Vuillemin E, Morère JF, Montestruc F, Mouri Z, Namer M. “The inconvenience and toxicity associated with the administration of multiple i.v. agents present significant and possibly prohibitve drawbacks to their use in heavily pretreated patients for whom *palliation and maintenance of QOL[Quality Of Life] are the primary goals of treatment.” *(Patients with terminal diseases usually need palliation. It’s a kind of care that is supposed to make you feel better, even though it can’t cure you. How many people going through chemotherapy say they feel better?)
The American Journal of Oncology Review, vol. 1 (3):169-70, 2002
Chemotherapy in the treatment of patients with metastatic breast cancer: high-dose, low-dose — what have we accomplished? By: Dr. Lawrence N. Shulman, M.D., Vice Chair for Clinical Services/Adult Oncology, Dana-Farber Cancer institute (Harvard Medical School), Boston “[over the past 20 years]… We relentlessly combined chemotherapy agents in various regimens, with ever-increasing dose intensity…as seen in this compilation of data, the survival for patients participating in these studies is exactly the same, less than 2 years. These four studies are a snapshot of hundreds of studies done throughout the world, spanning 30 years, utilizing innumerable combinations of standard dose chemotherapy without a hint of significantly improved survival..”
Health Affairs, The Controversy Over High-Dose Chemotherapy With Autologous Bone Marrow Transplant For Breast Cancer By: Michelle M. Mello and Troyen A. Brennan, September 2001 vol. 20 no. 5 101-117.
“HDC [High Dose Chemotherapy] gives the patient a concentrated dose of cancer-fighting drugs that have the effect of destroying the patient’s immune system…In the 1990s more than 41,000 patients underwent high-dose chemotherapy plus autologous bone marrow transplant (HDC-ABMT) for breast cancer, despite a paucity [deficiency] of clinical evidence of its efficacy…The results of five recent major randomized trials showed that HDC-ABMT offers no advantage over standard-dose treatment for breast cancer.
AP News, FDA: Avastin should not be used for breast cancer
Dr. Albert Braverman, M.D., chief of oncology at State University of New York Downstate Medical Center referring to Avastin for breast cancer. “The bottom line is that it doesn’t work very well, I’ve seen the occasional patient have a brief remission, which is nice, but it’s certainly not doing anything important. It’s not saving anyone’s life…I think a few years down the line it was becoming increasingly clear, at least to me, that this wasn’t a particularly active drug, despite the initial presentation…But people are sort of on a roll and it takes a while for things to die down.”
Austral – Asian Journal of Cancer, Vol. 4, No.4, October 2005. Surgery: A New Candidate to Explain
Breast Cancer Paradoxes? By: Riccardo Ponzone, M.D., Ph.D.
“…the principle of indiscriminate cell-kill by chemotherapy is a path that will take to nowhere…Furthermore, the “sleepy” attitude of single disseminated cells who early colonise distant organs through the lymphatic or vascular circulation, should discourage everyone from thinking that they can be eradicated with conventional chemotherapy.”
Breast Cancer Research & Treatment, (2011) 130:345–351
Lack of efficacy to systemic chemotherapy for treatment of metaplastic carcinoma of the breast in the modern era, by: IC Chen et al.
“Tumor response to systemic chemotherapy remains generally poor for MCB patients…According to our single-institute retrospective study, the response of MCB to systemic chemotherapy remains poor in the modern era.”
The Lancet, 1998; 352: 515–21. Randomised trial of high-dose chemotherapy and haemopoietic progenitor-cell support in operable breast cancer with extensive axillary lymph-node involvement.
By: Rodenhuis et al.
“Since high-dose adjuvant therapy did not even yield minimum evidence of a survival advantage over optimum conventional therapy and was associated with severe toxic effects, we strongly believe that this therapy should be given only in the setting of a randomised clinical trial.”