Leading to Non Surgical treatment of Breast Cancer in future
Non Invasive Carcinoma Breast like DCIS (Intra Ductal Carcinoma in Situ), LCIS (Lobular Carcinoma in Situ), Medullary Carcinoma, Adeno Cystic Carcinoma, Mucinous Carcinoma – forms almost 10% of Carcinoma Breast and are localized disorder treated by excision of lump, or mastectomy if large in size. No CT or RT is needed.
Alternative procedures like Cryoablation, Radiofrequency ablation, and High Intensity focussed ultra sound, can be used in small size tumor as most of these tumor are diagnosed in early stage with total ablation of tumor followed by R.T.It can be followed regularly and chances are in 90%, no recurrence will be there in 5 years period. In case of recurrence, it may be Invasive (60%) and to be treated as Invasive duct carcinoma as per protocol.
Cryoablation in early stage Breast Cancer, work is in progress as multinational trial – SAVELMS, KAUFF MAN, CS, WHITWORTH P. et.al. – ANN. SURGONCO, 2004, 11:542-9.
- Deanna ATTAI – head of trial group at Los Angeles for Cryoablation with liquid Nitrogen – says – this non invasive procedure done on more then 50 patients, tumor size around 2cm, followed for one year with no recurrence. He said following ablation, the antibodies to the tumor are formed to fight recurrence (DAISY SHAPIRO and BRUCE HENSEL – New way to cure Breast Cancer without Surgery being studied – Center for Breast Cancer. INC and American College of Oncology Group, May 26, 2010.)
One recent study in Norway suggest – as many as 66% of both Invasive and non invasive may be termed an ‘PSEUDO CANCER’, which if left alone would grow, then shrink and then disappear over the course of years.
Non Invasive Cancers disappearance is still higher.
It is a different study – as contemplated by many Cancer Institutions in USA – to “Wait and See” approach to a Cancer patient who fears death if not taken care by present mode of managements. Still few Institutions do wait and follow closely for 6 months to one year and found encouraging results.
Better drugs availability with very good response in regression of tumor mass to high % as seen in locally advance Breast Cancer. In few centres Neoadjuvant therapy response clinically shows complete response ,given Radiotherapy and adjuvant chemotherapy with follow up and survival as good as Surgery + RT
- RUBLION AND HARRIS – 1977, 1983
- VALAQUESS – 1983
- PERLOFF – 1983
During this period, higher chemo drugs and Target therapy drugs were not available but results were compatible to other types of management during that time.
National Cancer Institute USA –
Surveillance Epidemiology and End Result (SEER) – studied – Age wise V/s Cancer Patient Survival, found higher survival in late stage more than 50 years.
In stage III and IV – 5 years survival is 26% with Surgery, RT.CT.- 16% and No treatment 10%.
10% patients did not receive any treatment but 10%survived for 5 years while those received CT and RT survival rate was 16% – needs study as body inner system did manage the tumor regression for some time and progression later to cause death.
NCI – also explained that result depends upon
- Stage
- Tumor size
- Hormonal status
- Human Epidermal growth factor
Overall Survival (all stages and Age group)
- 10 years – 83.7% (2003- 2009)
- Using TAXOL and HERCEPTIN
This is marked improvement in overall survival 10 years back (49%)
– STEPHENAEBI – (Switzerland) – 2012 – 182 patients – Median Age 56 years.
– Median time of Recurrence – 5 years
Add – CT – 5 years survival – 88%
NO CT – 5 years survival – 76%
ER (Negative)- 5 years survival with CT – 67%
ER (Negative)- 5 years survival with No CT- 35%
ER (Positive) – 5 years survival with CT – 70%
ER (Positive) – 5 years survival with No CT- 69%
This study suggest two types of Disease Behaviour –
ER (-) – Poor result
ER (+) – Good result even not given C.T.
HORMONAD DEPENDANT TUMOR has some internal metabolic enzymatic inhibition process, checking Oestrogen metabolism is important in development of Breast Cancer.
16 alfa Hydroxylated Oestrogen metabolites is associated with increased risk of Breast Cancer. Oestrogen metabolism pathway – favours 2 – Hydroxylation over 16 alfa hydroxylation with reduced risk of Breast Cancer in Premenopausal women. The metabolic shift is due to PGC-1B /ERRY transcriptional pathway of cell proteome (Lillean – Cell Metabolism, Vol. 12, Issue 4, 2011).
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WOLMARK et.al. (2001_ – Women 49 years or less significant advantage on overall survival with Neoadjuvant CT – 71% v/s 65% 5 years, 55 years v/s 46% (disease free 5 years).
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International Journal of Surgery – Vol. 7, issue 5, 416-420, 2009
Moh. Ishtiaq Ahmed, T.W.J. LENNARD, – Neoadjuvant Chemo has brighten the survival in locally advance disease by 10 to 15%.
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FISHER et al. – Tumor Excision increases metastasis. Pre operative CT prevents these changes.
HORMOPNAL Therapy in hormones positive receptor cases with Target therapy has improved overall survival and recurrence free period. National Surgical Adjuvant Breast and Bowel Project (NSABP) – B-18 – trial (1523 patients – T1-3, No-1, Mo)
New Adjuvant – (CTX + DOXIR)
Clinical response – 80%
Complete response – 30%
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Pathological response- 13%
Results in Breast Conservation in all the patients and improve overall survival by 8%.
Europe Group Cooperative Trial (ECTO) GIANNI et.al. – 1355 patients – randomized trial
Neoadjuvant group –
Complete response – 23%
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ROBERT WASCHER of Cancer TREATMENT CENTER of AMERICA – 2012, Good Year – Arizona – Considering the Genetic cause of Cancer leading USA female (1 of 8) high risk to Indian (1 in 90) China (1 in 80), but second generation all in the same category of 1 in 8, presume other causes dominates than original genetic theory in all cases –
1/3 – life style
1/3 – Tobacco / Alcohol
1/3 – Obesity, , inactivity and DIET
60% cases are preventable by modifying life style.
METAFORMIN (Anti Diabetic drug) used commonly to check Diabetes, is a AMP Kinase dependent – growth – INHIBITOR for Breast Cancer cells.
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Moh. Zakir Khan, Ryan Dowbrig, I, George Fantus, Nabuns Sonebarg, Michael Pollak Cancer Research – 2006, 66(21), 10269-73.
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2% of Breast Cancer are due to gene BRCA-1 and BRCA-2 cell mutation.
Tp53 also adds in some cases with other disorders, PTEN gene also sensitive to Cancer Breast with Cowden’s syndrome (Breast Cancer – Research Dec. 1999)
DOI – 10, 1106/bcr6
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Known genes observed familial aggregation of Breast Cancer, and mother, sisters, daughters have double chances of getting Cancer Breast then normal population. It is CHANCE only not all such familial presence of BRCA 1-BRCA-2 gets Cancer Breast.
Question WHY – 2% of these genetic presence get Breast Cancer while others do not.
As seen in racial distribution of Cancer in USA, second generation has equal chance of getting Breast Cancer influenced by – Environmental diet and total life style.
PETO et.al. – The Prevalence of BRCA-1 and BRCA-2 mutation amongst early onset of Breast Cancer in U.K., J. Natl. Cancer Int. 1999, 91:943-949
30 mutations ( BRCA/1,BRCA/2) in 617 Breast Cancer patients only below the age-46. Only 5 of these 30 patient’s Mother or Sister had Breast Cancer while 64 relatives of 587- non Carrier (gene) patients had BRCA gene positive
Mutation in TP53 and PTEN is very rare and less than 1%.
What type of gene might underlie in the remaining 75% to 80% of familial Breast Cancer? Various possibilities studied like third gene influencing BRCA 1/2, linkage of oestrogen receptors on chromosome 6p or 8p. But no definite conclusion.
Lobular Carcinoma and Lobular Cancer in Situ show large familial involvement but no BRCA 1/2 but other gene, of low grade and sporadic only.
Similar such genes are identified and are more the tumor suppressor genes.
In familial Breast Cancer without BRCA 1/2, polymorphism likely to be single nucleotide polymorphism leading to amino acids substitution causing cell mutation in non essential Gene due to Gene coding and metabolism with metabolic changes leading to ATP Kinase activities and Non Glycolysis and cell mutation.
Early detection of Breast Cancer – in 95%of patients 30% localized to Breast and 70% nodal involvement and beyond.
Use of local radiation and adjuvant chemotherapy has improved local recurrence and overall survival. First time in USA and UK noted decrease in mortality due to use of Adjuvant chemotherapy (PETOR, BOREHAM J., CLARKEM, DAVIS C., ERAL Y. UK, USA breast cancer death down 25% in the year 2000 at ages 20-69 years LANCET 2000, 355-1822.
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Treatment plan has to be individualized depending on – Age, Size of tumor, tumor grade, nodal statistics, hormonal status HER2Nu – status.
Adjuvant C.T. in early stages has increased overall survival and median recurrence rate in years with newer C.T. of Anthracycline and Taxane with Tamoxifen or Aromatase inhibitor.
Neoadjuvant – regression of tumor followed by Surgery – R.T. and Adjuvant chemotherapy – increased overall survival by 10%. Remarkable observation in locally Advance Breast Cancer – is regression of Tumor mass by more than 30 to 40% by 2 cycle of C.T. Another 10% regression by 3rd cycle, followed by Surgery, Advance CT and R.T.
Question is – If more then 3 coruse of active C.T. is given chances are 100% regression of tumor. But such randamized treats are hardly any because of many reasons.
– Women – Consent explaining results and chance for early recurrence if Surgery not done.
– Legal problems
– Majority Patients do not agree for such trials.
Three trials done which proves that CT – complete regression, local RT/or only follow up – Disease free interval – 2 years in all group patients (Stage III/IV)
In Early Stage (I & II) – complete regression is seen in 2nd and 3rd cycle followed by Surgery and adjuvant C.T. with breast conservation. Difficult to get consent for C.T. only or CT+ R.T. and follow up.
More randomized trials, confidence of Surgeons and group doing trials and better cooperation and understanding among patients to follow protocol of Neoadjuvant CT and RT or No RT, – follow up for 5 to 10 years or till recurrence. No randomized trial found but few cancer registry documents did show a large number of patient who opted for No Surgery and received alternate treatment. These results were compared, though logically no match as far age, stage of disease or risk parameters are concerned.
HELENA M. et.al. – Patients Refusal of Surgery strongly Impair Breast Cancer Survival – ANN. OF SURGERY, Aug. 2005, 242(2) – 276-280.
Record of Geneva Cancer Registry – 5339 patient less then 80 years – No metastasis (1975-2000)
– 75 patients (1.3%) refused Surgery
– 37 patient (53%) – No treatment
– 25 patient (36%) – Hormone therapy alone
– 8 patient (11%) – Adjuvant CT with or without Hormone
5 years survival – Surgery + Adjuvant – 87% and who refused Surgery – 72%.
1- No Surgery – Women – older age group and large size tumor
2 – No Treatment –
– 5 years – 64%
– 10 years – 39%
In group received RT+CT+ Hormone 5 years survival 81% as good with Surgery 84% and 28% – 10 years.
There is a difference in level of Survival following surgery and other treatment, but high percentage upto 72% survival 5 years with minimal or no treatment. If this group is given a randomized treatment of proper, Neoadjuvant CT+RT and Adjuvant CT – might show equally good result.
COMMENT by Authors –
Hard evidence in the form of recent studies on the prognosis of non operated breast cancer is non existent.
BLOOM, J, RICHARDSON W.W, HARRIS E.J, – National history of untreated Breast Cancer (1805-1933).- Comparison of untreated and treated cases to histological grade of malignancy B.M.J. 1962, 52992-213-221.
250 Women( No treatment) – 5 years survival – 18% and 10 years – 3.6%.
Poor result then if Surgery added.
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Few series as below reported Non Surgical Management with R.T. C.T. and Hormonal treatment has as good result and % survival as with Surgery, RT/CT.
VAN LIMBERGENE, VANDER S.E., VANDEN B.W. et al.- Local Control of operable Breast Cancer by Radiotherapy alone. EUR J. CANCER – 1990; 20-674-679.
JACQUILLAT, WELL M, BAILLET F, et al. – Result of Neoadjuvant chemotherapy and Radiation therapy in the Breast conserving treatment of 250 patients, with all stages of Infiltrative Breast Cancer. CANCER ,1990; 66:119-20.
DUBOIS J.B, SALOMON A, GARY BOBO j, et al. – Exclusive Radiation therapy in Breast Carcinoma. RADIOTHER ONCO., 1991; 20:24-29.
JALQUILLAT C., WEILM,AUCLERE G. et.al. – Neoadjuvant chemotherapy in the conservative management of Breast Cancer, a study of 252 patients. RECENT RESULT CANCER RES. 1989; 115:36-42.
One study – Surgery after complete response with Neoadjuvant CT show No difference in survival but reduction in local recurrence.
GINGA, WEBB A., ASHLEY S., et.al. – Is surgery necessary after complete clinical remission following Neoadjuvant chemotherapy for early Breast Cancer. J.CLIN.ONCO. 2003; 21, 4540-4545.
