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Breast Cancer/ER PR Scores / Mitotic Activity / Ki67 score / prognoses.


Thanx for the time .My wife a month ago had a Modified Radical Mastectomy with level 2 Clearance. Her Surgical pathology results are as under
Tumour Size 1.4cms.
Infiltrative Ductal Carcinoma
Grade 2
( Tubule formation 2/3
Pleomorphism 3/3 , MITOTIC ACTIVITY 1/3)
SCORE 6 Bloom & Richardson .

Out of 22 lymph nodes tesyetested Only 1 positive for mets. mets size 0.8 cms perinodal spread positive.

Lympho vasvascular invasion present.
Fibroses moderate .

Estrogen Receptor Positive Score 8 ( Alred )
Progesterone Receptor Positive Score 7 ( Alred )


Ki67 : positive 44% .

My wife is 57 years old and is post menopausal.

I have become very concerned after the Ki67 reports becausbecause that suggests that it is a luminal B tumour which carries a poor prognoses.

However what i cant understand is the apparent discrepancy between the Tumour Grading specially the Mitotic Score of 1/3 and overall grading of Two and the Ki67 scores. I understand that thththth Mitotic Score is thd most objective parameter of grading as it is least observer dependent.Similarly how can one reconcile a pleomorphism of 3/ 3 with a Mitotic Score of 1/3 ? How can a tumour which is so pleomorphic show so minimal Mitotic Activity.

The other point is that from my perusal of literature the luminal B tumours are either low or moderate scoreres of ER and almost always PR negative. Whereas in my case the ER score is 8 and PR score is 7.

Im a Physician myself so i need the above issues clarified to know what is the prognoses .My wife has been recommended Chemo followed by Endocrine Therapy.

I will be grateful if you can opine on this. Regards.

ANSWER: Well, these different tests are DIFFERENT tests and not very much dependent of each other. Each of them has strong points and weak points. And again they ARE independent of each other. So based on them I can only conclude that I do agree with her doctors who do suggest chemotherapy and hormonal therapy. No treatment can offer guarantees but from the presented facts that treatment combination offers the best chances - and that is all anyone can offer - of success. So I do suggest that she follows their advice! Good luck!

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---------- FOLLOW-UP ----------

QUESTION: Thank You for your answer . In line with my initial question can a prognoses be offerred with some justification in the case or it can be said that the prognoses is uncertain ?
And moreover what is the credibility of predictive tools like predict.nhs and adjuvantonline .com both of which are giving a very good five and ten year survival statistics in this case ?


ANSWER: Well you do not seem to have been very satisfied with my previous reply so I am not certain that I will be able to satisfy you now either. I understand that this is a difficult moment in life for you and your wife but I can only answer to the best of my ability and answer as honestly and truthfully as I can. Being here I am also obliged to answer. One factor you do not speak much about is the stage of her cancer. Yes a metastase was found in only one single lymph node. But it was found and that makes this case a stage 3, and staging is important. Based on what you have told me I can not regard this cancer as not very malignant. I wrote before that these different factors are independent of each other. So I can not agree with your arguments that since one factor is less malignant another factor that indicates a higher degree of malignancy can not be right. The 2 important factors here are grade and stage. The stage must be considered a 3.
The grade has been set as a 2. While the risk of spreading of a cancer with the grade of 2 is lower than with a higher grade it is not 0. And here it has spread to as far as we know one of the examined lymph nodes. Why do we use these predictive factors. Not just for statistics but as guides to the best kind of treatment.
Aggressive cancers need aggressive treatments. So again I do recommend the treatment recommended by her doctors that is chemotherapy followed by hormonal treatment. That is the best use of the prognostic qualities of these factors. The prognosis without treatment is not good. But treatment along these lines will,without doubt improve it. Guarantees though can never be given. But that is true of most things. The predictive tools you mention have never been used by me - I retired after a stroke a little more than 12 years ago - so I have no opinion about them. However I am not only a cancer doctor, I am also a cancer patient - prostate cancer. My urologist told me almost 7 years ago that I should not worry about my high PSA level (8.8) since I had such an enlarged prostate that that alone was the probable cause of my high PSA, his computer told him that my risk of a prostate cancer in this situation was only 10%! I told him I was aware of that but 10% here was not a low risk. I wanted to KNOW so I demanded biopsies. When I came back for the biopsy results he looked like a wet cat. Of my 8 biopsies (needle biopsies) 5 showed cancer. They showed a Gleason score of 3+3 in 3 of them and 3+4 in 2 of them. After that I took command and demanded radiation therapy - only, no surgery at all. It seems to have worked. Now more than 6 years after the end of my treatment my PSA is still since the end of my treatment below 0.05. And I have had very few and easy side effects of my treatment. Good luck!

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---------- FOLLOW-UP ----------

QUESTION: Thank You very much.You have cleared some of the confusions but some remain. I have no doubts whatso ever that the treatment after surgery here is chemotherapy followed by hormonal therapy, being an internist mymyself. My questions are more academic if you may and are resting upon my need to be sure as to whether the histologhistology reports of my wife are totally correct or not.
But first please allow me to differ with your opinion that it is a Grade 3 Cancer. All the Oncologists and Pathologists i have consulted have labelled it as a Stage 2 B cancer by virtue of the fact that the tumour is less then 2cms and has involved One lymph node. Stage 3 is when the size is more then 2 cms and has involved more then three lymph nodes.

The other point which i am trying to seek clarification from the hisyopathologists and so far have not been able to find an answer is that both MITOTIC ACTIVITY and Ki67 are parameters which reflect on the degree of PROLIFERATIVE ABILITY OF THE TUMOUR. In other words both test the same characteristic. Now MITOTIC ACTIVITY is regarded by all histo pathologists as the most objective criterion in the grading of a tumour and indeed some authors and i will give you references go as far as to say that just the Mitotic Activity is enough to gauge the grading of the tumour , leaving pleomorphism and tubule formation aside.

Now my wifes Mitotic Activity was asessed twice by different observers one from the biopsy specimen and one from the surgically removed specimen and on both occassions the report was 1/ 3 which is the lowest or the minimal possible score.

Keeping that in mind , it has come as a surprise to the pathologists that the Ki67 result was so high 44% which is diametrically at the other end of the spectrum. Now the explanation which the histopathologists are giving me is that Ki67 has issues with standardisation internationally and no two labs in the world give identical results on this test on the same specimen. In fact the literature reports that the margin of error or the False Negatives or False Positives can be as high as 25 %. Keeping this in mind i wonder whether it would be advisable to have the Ki67 test repeated again or reviewed because the Ki67 test differentiates ER positive tumours into Luminal A tumours wwhich have an excellent prognoses and in which these days there is a debate whether chemo shoshould be added to hormonal therapy despite being lymph node positive if sixe is less then 2cms or Grade 2. Or even some authorities go as far as Grade 3 if the Oncogene 21 test confirms it. On the other hand the Luminal B tumours do not have as good a prognoses as Luminal A tumours and require chemo therapy and endocrine therapy , both.

So these are some academic issues which are agitating my minmind notwithstanding the fact that my wife is scheduled to recieve her first cycle of chemotherspy this week.
Regards and Thanks.

Thanks! To answer your academic questions I would need to be a patologiskt myself, which I most certainty am not! Yes I have done pathology work but that was almost 40 years ago. So I must ask you to direct your question to an expert of pathology.  With regards to the stage I will not argue  over 2b or 3 as the practical therapy result is the same so I prefer to call both 3. It is never wrong to ask for a repeated test, so by all means do that! Good luck!  P.S. My PSA being below 0.05 is not even measurable.

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Breast Cancer

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Claes-Gustaf Nordquist, M.D.


I`m a doctor of medicine and a specialist in radiation therapy and medical oncology. I have long experience in diagnostics and treatment of breast tumours.


I'm a Doctor of Medicine and specialist in Medical Oncology and Radiation Therapy educated & trained in Sweden. Now retired. Background in Radiation Therapy, Medical Oncology, Radiation Protection, Nuclear Medicine, Diagnostic Radiology, Gynecological Oncology, Clinical Pathology, Clinical Cytology,Hematology and Internal Medicine. M.D. from the faculty of medicine, Royal Karolinska Institute, Stockholm, Sweden. Have also been an exchange student at the Hebrew University, Hadassah Medical School, Jerusalem Israel. Former medical consultant, Swedish National Board of Radiation Protection. Former Police Surgeon and Medical Examiner, Stockholm Police Department. Former Chief Medical Officer, The Royal Guards, The Royal Horse Guards and the Royal Household Brigade, Royal Swedish Army Medical Corps.You can also reach me on: I have no restrictions on the number of questions there.

I also answer questions about Oncology (General Cancer), General History, Military History, Brain Tumors, Colon Cancer

I'm a medical doctor and specialist in medical oncology and radiation therapy.

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