Carcinoma of Breast known since renaissance hundreds of years BC to the modern science, undergoing changes for better from its basic understanding to its present management.
I explained my small data’s of those cases, left from the treatment group for various reasons, and compared with many such publications to find some astonishing result indicating some change in our basic perception and management to develop new management strategies with better results.
More than 15,000 cases operated/treated in last 50 years of which 4 years in USA Roswell Park Memorial Cancer Institute, Buffalo, N.Y. has given comprehensive idea of this disease and changing its character of Management from Radical to Extra Radical to Modified to Conservative Management. Role of other modalities of treatment – Chemotherapy, Radiation, Immunotherapy, Target therapy has given tremendous changes with more understanding of Cancer Cell Molecular Biology
From 2003 to 2017, in last 14 years after my retirement from M.G.M. Medical College, Indore. I and my colleagues operated 368 cases and followed for variable period of time from 5 to 10 with results comparable as in literature.
Those patient who refused Surgery for various reasons were treated only by other mode of treatment (CT+RT+Horm and few with Target therapy) with equally good response comparable to literature and comparable to Surgery+CT+Rt+HoR.
– Total No. of patients – stage wise – all age group
I – 44, II& III – 238, IV – 86
– 217 between 40 years and 60 years. 20% with more aggressive nature clinically.
Stage I – 6 patients did not agree for any surgical intervention younger age group (30-50 years). Received CT/RT/Horm treat with CR in all followed for 7 years.
Stage II & III – Out of 238 patients, 21 patients refused Surgery (10 younger age group 30 – 40 years, 11 more than 50 years). Treated aggressively without Surgery with CT/RT/Horm + Target therapy with comparable result of 5 to 10 years survival. 11 patient CR-6 years, 4 patient + Target Therapy – CR-5 years, 3 patients died of disease within 2 years, 3 patients did not turn up after-1 year. 15 patients alive more than 6 years out of 21 patients (71%)
Stage IV – 86 patients – large number of patients (25) did not continue treatment and lost to follow up. 49 patients were treated as per guideline with 4 years survival – 19 patients.
12 patients refused Surgery and treated with CT/RT/Horm/Target Therapy with reasonable response. 6 patients followed for 4 years with good response and alive. 4 patients died within 2 years and 2 did not continue treatment.
Total No. of patient 368 out of which 39 patient of all stages and all age group, did not have any Surgery but treated with Chemotherapy, Radiation and Hormonal therapy as defined. Used Target Therapy with better response in 8 patients.
Out of 39 patients, 23 patient had good response with disease free period – 60% 7 years. Stage 1- 100%-6 years, II & II – CR-7 years- 52%, CR – 4 years – 19.5% and IV-50% – 4 years, 25% – 2 years.
These are the result of non-randomized study, grouped those without Surgery with other treatment. The result are comparable with any randomized study and accepted guideline of management.
If a well knitted randomized study is carried with accepted guideline versus nonsurgical treatment with full understanding a future answer to guide Cancer Breast Management can be arrived.
Literature and past history search among those articles which treated Carcinoma breast patients left out of randomized study gives a positive ray of hope without Surgery with equivocal results and guide to improve with better understanding of epidemiology and molecular biology.
Carcinoma Breast had been described as bulging tumor of Breast with no cure in Egyptian Literature 1000 B.C. Hippocrates (B.C. 400) described four HUMORS of which Black discharge with irregular mass called as CANCER KARKINS – a Greek word for CRAB.
17th to 20th Century Excision of Breast mass/removal of breast with Excision of Axillary nodes remain prime treatment with variable results. Halstead (1886) postulated Radical Mastectomy, a Gold standard for almost a century with little better survival rate around 50% – 5 years.
George Beatson (1895) – described shrinkage of tumor after oophorectomy. Following this Adrenals/pituitary excised to remove other source of oestrogen with some comparative better result.
George Crile (1955) Bernard Fisher (1976) – postulated Ca Breast as Generalized disease. Start of Radiation to control local Breast disease and Chemotherapy for disease in rest of the body with improved survival by 20%.The change in improve survival of all age and stage group seen due to role of RT and Chemotherapy.
Marie Pierre Curie (1904) discovered use of Radiation in Cancer, control it locally only. Newer techniques resulted in its use commonly in Primary as well Secondary management of Ca-Breast. It resolves tumor mass to zero depending on tumor load, helpful as adjuvant treatment with effective result.
Genetic theory of Cancer Breast is prevalent since 1950’s. With isolation of BRCA-1 and BRCA-2, scientist diverted research to genetic control and its impact on management. Only 20% of Cancer Breast has BRCA 1 and 2 genes and only 2% of general population has BRCA 1 and 2 positive. Racial dominance of Ca-Breast more in USA/ Europe and (1 in 8) less in India and Mongolian lace (1 in 90 to 900), thought to be genetic, but such racial people living in USA, second generation has same percentage, due to DOMINANT ENVIRONMENT FACTOR, including Diet, Tobacco, Alcohol and Living Habits.
These factors work as Carcinogens / Co Carcinogens and causes body metabolic changes and cell mutation and cancer.
BRCA-1 and BRCA-2 are suppress gene with functional amino acids. Loss of these functional amino acids deregulate suppress genes forming Pyruvate Kinase – M2, and develop Cancer, through Anerobic way of getting energy (Oxygen) – calling GYCOLYSIS (WARBURG EFFECT).
Dominant role of cell metabolism resulted in chemotherapy drugs to control metabolic process at various level of cell cycle and target specific the mutation cycle to kill cancer cells.
Surgical procedures did improve survival and morbidity in early stages, but overall survival in late stages (III and IV) more or less remains the same inspite of RT and CT till 1980’s.
Locally advance breast Cancer (Stage III-III-B) responded well with Neoadjuvant CT down grading size followed by Surgery RT and CT, caring for local and distant metastasis. Improved survival by 50% to 70%, Median survival time 4.9 years (M.D. ANDERSON, 2006).
Hormone receptors made a difference in management, with poor response to negative receptor. Drugs like TAMOXIFEN (Oestrogen receptor Inhibitor) and AROMATASE – Inhibitor blocking Oestrogen synthesis and regression of tumor cell, confirm metabolic / hormonal influence on Ca-Breast Tumor mass. It helps in PREVENTION of Ca-Breast in high risk – group.
National Cancer Institute (USA) – explained the result depends upon – Stage, Size of tumor, Hormone status and Human Epidermal growth factor.
Result from (2003-2009 all stages and age group) – 10 years – 83.7% TAXOL + HERCEPTIN while from 1995-2003 with other chemo drug 10 years survival 49% only.
STEPHEN AEBI (Switzerland-2012) – 162 pts Median Age – 56 years, Median time Recurrence 5 years
5 Years survival all stages/all age group -Surgery or Surgery + CT – 75% to 88% in ER+, while it comes down to 35% in ER -(negative)
Role of Oestrogen receptor shows biological behaviour of tumor and in series – Tamoxifen alone given 40% 5 years survival.
– FISCHER et.al. (1990) Surgery(All types) alone survival is same since last 50 years around 45-50% but CT as Neoadjuvant and Chemo after Surgery improved survival by 10%-15%.
Target therapy + Hormone therapy in Oestrogen positive cases – high survival 80% – 5 years and recurrence free period – 5 years – 76%. (National Surgical Adjuvant Breast and Bowel (Project (2004) – NSA BP – T1 T3, No-1, Mo)
1523 patients Drugs – TAXOL + DOXYRUBICIN – clinical response 80% 5 years, complete response – 30%. Associated Breast Conservation – result improved by 10%.
– CLARKE et.al. LANCET -2000: 355, 1822
– Early detection Cases – 30% localized in Breast while 70% has Axilla involved.
– Neoadjuvant CT + RT – complete regression of primary tumor – followed by Adjuvant CT
– While Breast Conservative Surgery + NeoAd + RT + Adjuvant CT – 88% – 5 years survival and Breast Cancer death down by 25%
HELENAM et.al. (ANN OF SURG – Aug 2005 242(2) 276-280) –
Patient’s refusal of Surgery impairs Breast Cancer survival but still around
20% – 30% 5 years No CT given
GENEVA Cancer Registry – (1975-2000) – 5339 patient
– Refused Surgery – 75(1.3%), 37 patient – No treatment, 25 patients (36%) – only Hormone Therapy and 8 patient (11%) – CT + Hormone.
– 5 years survival 72%
– In other patients- underwent – Surgical management + CT
– 5 years survival 87%
BLOOMI et.al. (BMJ – 1960: 52992, 213-221) – National history of untreated Breast Cancer (1805-1933). Comparison of untreated and treated cases to histological grading of Malignancy.
250 Women – 5 years survival – 18%
– 10 years survival – 3.9%
VAN LIMBORGENE et.al. – Local control of operable Breast Cancer after Radiotherapy alone. EUR.J. CANCER – 1990, 26 – 674-679.
– Non Surgical Management of Breast Cancer with RT, CT and Hormones with equal good survival % and recurrence free period as with Surgery + RT+CT.
RINGA et.al. – Is Surgery necessary after complete clinical remission following Neoadjuvant CT in early Breast Cancer? J.Clin. Onco. 2003, 210, 4540-4545.
Surgery after complete response with Neoadjuvant chemotherapy shows no difference in survival but reduction in local recurrence.
Suggests – RT – after complete response to get same good result.
JACQUILLATET et.al. – Result of Neoadjuvant chemotherapy and Radiation in Breast Conserving treatment of 250 patients with all stages of Infiltrative Breast Cancer.
CANCER – 1990, 66:119-29
Results are comparable to Conservative Surgery/CT/RT.
ROBERT W. et.al. – Cancer treatment Center of America, Good Year, Arizona-2012.
– 60% of Breast Cancer can be avoided or prevented by MODIFICATION OF LIFE.
CUZICK J. et.al. – Over view of the main outcome in Breast Cancer Prevention THE LANCET, 2003-361:9354, 296-300.
ER (+) cases TAMOXIFEN – 48% reduction in disease.
METFORMIN – diabetic drug is a AMP Kinase dependent growth Inhibitor for Breast Cancer.
MAHAVESH ZAKI KHANI et.al. – Metaformin inhibits gluconeogenesis in hepatocyte and epithelial cell and AMP Kinase inhibitor – CANCER RESEARCH – 2006: 66, 21, 10269-73.
HAMEL P.J. et.al.- Non Surgical Breast Cancer treatment – CENTRAL HEALTH -2014.
NORWEIGIAN STUDY – 66% of Non Invasive / Invasive Breast Cancer are slow growing and called case “Pseudo Cancer” if left alone, shrinks and may disappear. WAIT and SEE, if progression Chemotherapy/Radiation combination diminishes tumor completely.
ONCOLOGISTS AND PATIENTS- FEAR OF DEATH and take routine course of mandated treatment fully knowing result and survival has not changed much in last five decades – 50% – 60% overall.
Better Result following Target therapy in HER2Nu positive patients, and
TARGET + TAXOL in all group.
NCI (USA-2014) – 123 – randomized trial (100,000 – women) Meta analysis.
Chemotherapy overall improves Survival and risk of dying from Cancer by 30%.
REFERENCES
- Bernard Fisher, Joseph Constantine, D. Lawrence, Wickerham, Carol K. Redmond, Maureen Kauanoh, Walter M. Cronin, Victor Vogel, Andre Robidoux, Nikolary Dimitrax and James Alkini. – J.Natl. Cancer Institute – 1988, 90(17): 1371-1388
- Bloom J., Richardson W.W., Harie E.J. – Natural History of Untreated Breast Cancer. – BMJ-1962, 529 92 :213-221
- Geneva Cancer Registry (1975-2000) -5339 Patients : Review Report.
- Hamel P.J. – Non Surgical Breast Cancer Treatment. Avoiding Knife .-Health Control.Com. Sept, 22, 2011.
- Helena et.al. – Patient refusal of Surgery strongly impairs Breast Cancer Survival. – ANN of Surg, – Aug. 2008,: 242(2)- 276-280
- King A, Weble A, Ashley S., et.al – Is Surgery necessary after complete remission following Neoadjuvant Chemotherapy for early Breast Cancer. J. Clin. Onco. 2003, : 21, 4540-4545
- Moh. Zakir Khan, Ryan Dowbug, I, George Fantus, Nabum Sonebarg, Michael Pollak. -Cancer Research – 2006 : 66(21) 10269-73
- National Cancer Institute Report (2014),- 123-Randomized Trial Meta analysis.
- Peter R, Barcham J., Clarke M., Davis C, Beral Y.- UK USA Breast Cancer death down 25%. Adjuvant Chemotherapy., Lancet – 2000,: 355-1822-24
- Van Limbergene E, Vander, S.E., Vanden, B.W. – Local Control of Operable Breast Cancer with Radiotherapy alone. Eur.J. Cancer, 1990, :26-674-679
Dr. Satish K. Shukla
M.S., F.I.C.S., F.A.C.S., FRCS, Oncologist (USA)
President, Association of Surgeons of India (2014)
Director, Lakshmi Memorial Hospital and Research Centre, Indore
Professor & H.O.D. Surgery (Retd.) M.G.M. Medical College & M.Y. Group of Hospitals, Indore
Chairman/Chief Editor Indian Journal of Surgery (2003-2013)
Governing Council Member ASI (1991-97)
President, Indian Association of Surgical Oncology 1993
Medical Scientist of the Year LIMCA Book 1996
District Governor Lions Clubs International Dist. 323-G1 (2004-05)
Associate Editor – The Lion Magazine International (2013-15)
Chairman – Managing Committee, K.K. College of Science & Professional Studies
Chairman – Managing Committee, K.K. Nursing College, Indore
ICON SURGEON OF SAARC Nations – SAARC Surgical Society 2015
SAARC – ASEAN Coordinator Teaching and Learning Programme 2014-17
Life Time Achievement Award – 2017 Association of Surgeons of India
