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Wednesday, September 22, 2010

10.16 Secrets of Good Breast Cancer Survival

Physician's Notebooks 10 - http://physiciansnotebook.blogspot.com - See Homepage


16. Breast Cancer.  Update: 22 Septr 2021
Screening
Diagnosis starts
Treatment for breast cancer starts
If the breast cancer is "Curable,"
The Axillary Lymph Nodes in Breast Cancer Prognosis and Prediction
Adjuvant treatment means
Hormonal Adjuvants
Chemotherapy consists of
 Monoclonal targeted antibody treatment is
The experimental work from 1998, in node positive, worse prognosis
Metastatic Disease
Many factors affect survival in metastatic breast cancer
Summing up with Example Cases
In situ breast cancer
The importance of self-psychoanalysis
Causes, Promoters and Prevention - a Practical Summing Up
 The future of breast cancer treatment
A new case 
Screening
 is for finding lesion when you are in an apparently normal condition - no lump, no thickening, no skin lesion, no symptom in breasts and no abnormal past imaging.
   A positive screen for breast cancer is not diagnosis; that needs diagnostic testing. In 2021, x-ray mammography starting age 40 once a year is standard for screening and for testing and has given 4-yr lead in picking up cancer. But the x-ray mammography for screening is not 1 or 2 x-rays. It is yearly from age 40 for life.
   Data show a slight increase in cancers from it.
   I have my doubts about x-ray mammography for routine screening because a person goes into a screening with no known breast disease and in most cases is not high risk and, in my opinion, the program should have no risk. Still, that is the standard at present.
   In my opinion, breast cancer screening should start at puberty with monthly self breast exam plus doctor doing annual breast exam. A worrisome symptom or abnormality needs a consultation by M.D. breast cancer specialist and if imaging is needed, it should, first, be ultra-sound and, if positive and needle biopsy is not called for or the symptom persists despite a negative ultrasound echo, it should get MRI imaging for breast cancer. (But that is a minority opinion!)
   In women who are high risk for breast cancer (Parent, sibling or child with breast or ovarian cancer; or the person herself with previous breast or ovarian cancer, or using female hormone regular medication like birth control or relief of menopause.) the advised x-ray mammography is OK in my book; alternatively a first ultrasound breast screening should start at age 25. For the usual person, it starts at age 40.
   Ultrasound (US), because harmless, inexpensive and easily done, may be repeated at short intervals as many times as one chooses. That is its power.  But it has low sensitivity to pick up cancer. Breast MRI is highly accurate and safe but expensive and inconvenient so it should be reserved for backup imaging.

Diagnosis starts as soon as you notice a symptom or sign of breast cancer like a lump, a pain, a discharge from nipple, or get a positive mammography imaging result by x-ray, ultrasound, or MRI.
Whether you do screening without x-ray by US and MRI or standard screening by x-ray, the next step after a positive screening should be to make the decision who and where to consult. For starters in USA some major centers are Sloan-Kettering in NYC and Massachusetts General in Northeast; or the MD Anderson Center in Texas, and the Mayo Clinic in Rochester MI.
   Diagnosis is to confirm you have a malignant breast lesion. In 99% of cases it will be cancer (epithelial malignancy). Diagnosis often starts with special x-ray mammography views and utilizes US and sometimes MRI.
   Diagnosis confirming cancer should show its histology (ductal or lobular, grade of malignancy I to IV), its degree of invasiveness (in situ or invasive) and stage of spread (I to IV with Tumor size, Node plus or minus and Metastasis a.k.a. TNM status). Diagnosis should include Estrogen and Progesterone Receptor status (ER and PR + or -) and special growth factor status (ERBB + or -). And as will be mentioned in end note, increasingly, the most modern care facilities should have a gene array of prognostic (Course of disease in years expectancy) and predictive (Chances of cure from various treatments) factors.
   Diagnosis is by biopsy, which may start with fine needle aspiration (FNA) or go to core needle biopsy (CNB) or (rare in 2021) open excision biopsy. Here you need to go by expert advice. A CNB will be needed for full definitive diagnosis with all prognostic and predictive factors and gene array tests.


Treatment for breast cancer starts once diagnosis is complete. It needs a decision on place of treatment and keep in mind that treatment may be many-year including management of dying/death. Seminar based, non panicky, unhurried decision is best. Even with definite diagnosis of invasive cancer, taking up to one week to make a good decision on treatment is better than panicky rush to poor treatment.
   A treatment plan should start with answer to basic question: Is the cancer curable? (Occasionally, "curable" cases turn out "incurable") Or incurable? (Occasionally, "incurable" cases are cured)
  "Curable" here means a breast cancer that after testing is found to be localized to the breast with, at most, spread to 4 or less axillary (underarm) lymph nodes on same side.
  "Incurable" here means breast cancer with metastasis outside of same side axilla (underarm and note number of affected nodes).


If the breast cancer is "Curable,", the essential treatment should be surgery (Chemo- or endocrine assists may be started pre-op). In 2021, two choices: removal of the whole breast and may include removal of underarm lymph nodes on same side. Or breast conservation a.k.a. lumpectomy removal of the breast lump containing the cancer with a 1- to 2-cm tumor-free margin and followup radiation treatment and may include axilla lymph node dissection and breast reconstruction.
   Today, keep aware that pressure for lumpectomy exists among lay public. Studies going back to the 1980s show no curative advantage for lumpectomy over mastectomy but the concept of the breast as a woman's body image object has made breast conservation sought affected by breast self image and accept
   I have made love to a woman after a radical mastectomy and a missing breast and found her just as desirable and satisfying as with breast intact. The price you pay for breast conservation or reconstruction in breast cancer treatment is (In my opinion!) too much too soon to justify it. There are, of course, cases where a reconstructed breast is important to the life and for these patients; then, by all means, seek it and get the best.


The Axillary Lymph Nodes in Breast Cancer Prognosis and Prediction As part of treatment, the status of same-side axilla lymph nodes for positive cancer cells must be determined. This is best done before (or at start of) definitive surgery. Till recently this involved a complete dissection and removal of the underarm nodes but today in 2021 it should start with sentinel lymph node test, in which a blue dye with radioactivity is injected into the investigation olved breast and only underarm lymph nodes that show the radioactive dye are dissected out for exam. No nodes showing blue with radioactivity means no node dissection. And even if positive nodes are dissected, the surgery is often less than with complete node dissection. When a dissected sentinel node shows cancer cells, a complete lymph node dissection may be needed. By the use of the sentinel node technique over 90% of node dissections are avoided.
   A patient with a diagnosed breast cancer and no involved sentinel node has 90% or more chance of ten-year cure after mastectomy alone or after lumpectomy with radiation. When up to 4 nodes are involved curability chances are less but still quite high. Above 4 involved nodes, curability chances drop to less than 10%. Size of the breast tumor is important. Less than 1 cm diameter has best prognosis; 5 cm or more has poor prognosis regardless of lymph node involvement. Also histology is important: Grade I very good prognosis; grade III or more, poor. The combination of smallest tumor, no nodes and grade I is best with cure rate after mastectomy alone 95+%.
   The need for radiation right after a mastectomy will much depend on tumor size and grading and whether or not a positive node is discovered. With small, low-grade tumor and no positive nodes, some surgeons may not advise radiation. 
   Lumpectomy always has radiation advised with it and statistics show the post lumpectomy radiation sharply improves 10-year cure rates.
   Radiation is a series of daily to weekly treatments that should be done at top radiation treatment center because special technique is needed to minimize inclusion of heart and lungs in radiation field.


Adjuvant treatment means additional treatment that assists cure or good result. Adjuvants improve the surgical result but alone would not cure. Adjuvants include hormone, chemo, and monoclonal-antibody (a.k.a. targeted therapy) drugs.
Hormonal Adjuvants have greatly improved survival after surgery with or without radiation. In 2021, it means taking the partial anti-estrogen Tamoxifen pill (or similar drug; an alternative is surgical removal of ovaries) for 5 years in pre-menopausal and menopausal women and an aromatase inhibitor (Anastrazole) instead of Tamoxifen after menopause. Hormonal treatment is effective only in ER+ or PR+ breast cancers. The specifics should be discussed with your oncologist.


Chemotherapy consists of cytotoxic drugs: the older standard regimen (CMF= cyclophosphamide/methotrexate/5-fluorouracil), the next generation anthracyclines and the latest taxanes. In contrast to hormonal adjuvants, which are effective but only against ER+ or PR+ (most effective against ER+ & PR+) the cytotoxics are less effective against all breast cancers but a bit more effective against hormone negative (ER -, PR -) breast cancer. And they are more toxic - the CMF causes hair to fall out, vomiting and nausea, depresses the white blood cell (WBC) count and immunity against infection and depresses brain function; the anthracyclines seriously affect heart function sometimes with terminal heart failure; and the taxanes cause muscle aches and weakness and low WBC count.
   Chemotherapy is given as a mix of oral and IV over 4 to 6 months several-day sessions a month so total course is close to a half year. The data show 1 in 3 women get 10 years disease-free and 1 in 10, longer survival.
   In low risk curable cases (no positive sentinel nodes, tumor size less than 3 cm, low grade I or II histology), chemotherapy may be avoided. But better to have at least one course because curability takes a long time to determine. Chemotherapy is used as last resort in incurable cases.

 Monoclonal targeted antibody treatment is the latest adjuvant. A number of breast cancers on biopsy will show the positive growth factor ERBB2. Before targeted therapy, the biopsies were often not tested for ERBB2 and even today in many cases the test is not accurately or carefully done. Since the advent of targeted therapy the ERBB2 test and its accuracy have become important for optimal treatment that gives longest disease-free survival. The test is usually done by immunohistochemistry (IHC) that gives 3 levels: strong +, equivocal +/- and strong negative. Also it is done by fluorescent in-situ hybridization (FISH), which is more complex but more quantitative and more accurate. The targeted therapy used since 2017 is Trastuzumab (Tzb)  a monoclonal destructive antibody against the ERBB2 growth factor. Tzb literally seeks out and destroys only cancer cells that have the ERBB2 molecule (and the more ERBB2 they have the better it works) as surface marker. It is thus a very specific destroyer of cancer cells. 
The experimental work from 1998, in node positive, worse prognosis breast cancer after surgery and just after courses of different cytotoxic combinations that used one in several-day-a-week course for 1 or 2 years shows it improves disease-free survival. But even its addition cannot cause cure because a percentage of even ERBB2 positive tumors have native resistance and the rest develop resistance after 1 or 2 years Tzb. It may be a useful adjuvant for some ERBB2+ cases. The Tzb therapy is presently started after surgery, radiation and combined with cytotoxic regimens and continues for a year or two with 3 times a week treatments.  But 2 side effects are a problem:
 1) Weakening the heart to the extent of heart failure in low percentage of cases so it should not be used with anthracyclines, which also weaken heart.
2) Increase of brain metastases compared to control group that got no Tzb. 

 In incurable breast cancer where the metastases show ERBB2 strongly positive, Tzb may be a useful addition to prolonging good quality of life.

Metastatic Disease does not include same-side axilla lymph node spread, which is considered part of curable local disease but still badly affects prognosis and choice of treatments. In 2017, in USA 3% to 5% new breast cancer patients had metastatic disease and the median survival was 18 to 24 months with 2% still alive 20 years after diagnosis. (If you are age 60, that is good survival.) Metastases most commonly involve the bones and skin followed by liver, lungs, brain (most feared with reason). I watched my wife die from a liver metastasis; it did not obstruct the bile and was a several-week not bad descent into hepatic coma with an ending helped by an IV morphine drip.
   Treatment of metastatic breast cancer could include a simple mastectomy; it does not cure but it may improve quality of survival. In cases where a single metastasis can be shown by careful testing, mastectomy plus removal of the metastasis may, rarely, cure. (Brain, liver and lung cases have been cured this way.)
   Continuing with surgery for metastatic cancer is the famous first reported case of ovaries removal in Glasgow on 15 June 1895 in a 33 year-old still-menstruating woman six months after metastasis of breast cancer to the chest, and this woman had documented complete disappearance of the metastasis and symptom-free life for the next 49 months (4+ years) until recurrence that caused death 2 years later (6+ years survival). The principle of ovaries removal is it works best in pre-menopausal case with ER+ metastasis.
   Hormonal adjuvants are useful for ER+/PR+ metatases, The various types (Estrogen, Progesterone, anti-estrogen, aromatase inhibitors) can be varied and sequenced to keep an incurable breast cancer case alive with not too bad quality of life for many years. Here the key is top care at best institution.

Note that in treating metastases with adjuvants it is important to test a tissue sample from the metastasis for ER, PR and ERBB2 receptor status even if the original biopsy was already tested, because the receptor statuses may change after a metastasis and this may affect tumor response to treatment. This explains why 50% of originally ER+/PR+ breast cancer tumor metastases do not respond to hormonal treatment.  

Many factors affect survival in metastatic breast cancer. The most ideal patient to survive with metastasis and good quality of life is ER+, PR+, ERBB2+, younger, no vital organ metastases (bone or skin mets only), free of other illnesses, good psychological outlook, and long relapse-free interval since last treatment. This is the patient for 20-year good quality survival.

Summing up with Example Cases: The reader to here has gotten a lot of data but may be confused as to what she may experience if she gets breast cancer. I give below two examples of curable breast cancer which you can consider best and worst outlook. Keep in mind "curable" here means the cancer confined to breast or at most to underarm same-side 4 or less lymph nodes, with curability worsening badly as more positive same side underarm lymph nodes are counted, as tumor size gets larger and as grade of tumor from I to III and each factor independent of the other.
   Case 1: you are 41-years-old, still menstruating and you get a notice your recent mammography positive. You go back for diagnosis, and a core needle biopsy in clinic or office shows invasive ductal carcinoma of breast that tests ER+, PR+ and ERBB2 -.  It is grade I (lowest malignancy). The tumor is measured between 1 and 2 cm (relatively small), You agree to sentinel node investigation and no nodes pick up the radioactive blue dye. Special tests show no cancer cells in blood, bone marrow and key organs. Your status is a small, low-grade, node negative, hormonal sensitive, ERBB2 negative cancer without demonstrable metastasis. This puts you in the most curable category. Your cure probability with either mastectomy without radiation or lumpectomy with radiation is better than 90%. The addition of 20 mg tablet Tamoxifen from the time of surgery daily for 5 years will add another 5+%. A 4-month course of cytotoxic chemotherapy might add another 2% to the cure rate.
  
Case 2: You are a 67 year old woman who feels a lump and imaging shows a curable breast cancer - size 5 cm, ductal invasive, histology III and ER-, PR- and ERBB2+. 
A sentinel node biopsy is positive for 4 nodes. A metastases check is negative.
   Case 2 is worse prognosis, potentially curable cancer. For starters cure is best achieved with mastectomy and complete same-side underarm lymph node dissection and removal. Hormone therapy is useless. A 4- to 6-month course of best cytotoxic therapy is useful. The question of Tzb treatment should be considered. It increases probability of 10-year survival but at increased risk of complication. In a 67-year-old, the odds do not favor its use because of the lesser life expectancy. But if Case 2 were a 41-year-old, Tzb makes more sense. (This shows the sliding scale effect of many factors in patient decision for therapy)
   Cases 1 and 2 are the two extremes of curable breast cancer and many will fall in between. But I think these two cases give an idea of the route to follow. Do everything in consultation with your oncology, surgical and other experts but my point is that the Notebooks patient keeps basic control of her case by her ability to just say No if she decides based on her knowledge not her fear that the course will not be good for her happy survival. At times she may opt for greater risk of cancer recurrence rather than opting for less risk with unhappy survival.


In situ breast cancer is diagnosed only by local biopsy with minor or no symptoms; it is pre-invasive and has best prognosis. It is usually cured by lumpectomy and may not need radiation but may be advised to use Tamoxifen if Er+, PR+. It should have sentinel node test because occasionally it may be node positive which takes it out of in situ and into invasive curable category.

The importance of self-psychoanalysis, I cannot over-emphasize. Get your own honest answers to your questions: "What are my reasons for desiring to continue to live with symptom-loaded cancer other than just staying alive?" "What losses in quality of life will I not tolerate?" "What are my responsibilities to caregiver, friend, sex partner and family member?" These are key questions and they apply not only to breast cancer but to all mortal disease. Entertaining, fictional reads relating to this and to breast cancer dying can be got by clicking 12.33 Dear Miss - Could You Help Me to Die? and


  • 16.(10-11) Nina's Breast Cancer
  • 16.(12-14) Dying of Breast Cancer
  • 16.(15-17) Palliative Surgery/Chemotherapy/Radiat...
  • 16.(18-19) Descent into the Valley  .

  • Causes, Promoters and Prevention - a Practical Summing Up
    This is practical: to give ideal advice to a women starting out in life so she has smallest chance to get and to die of breast cancer. There are no absolutes; each women fits the advice to her life.
       Age is key. The younger you are the more important is avoidance of cancer factors.
       Radiation: Avoid or, if not possible, reduce it unless benefits justify risk. It includes x-ray, radioactivity, cosmic rays (high altitude), radon gas (cellar living), excess close TV watching and passing through full body airport searches that use x-ray at US airports. But do not worry about cell phones, overhead power lines, ultrasound, MRI and magnetic fields; all have been checked and ruled out as cause of breast cancer.
       Aspirin or NSAID: if you have other need for it, be happy to use it because it lowers risk of breast cancer. But keep single dose not more than 1 adult headache pill, 325 mg Aspirin or, 500 mg acetaminophen (Tylenol) a day and be aware of its potential to cause bleeding (Aspirin) or liver damage (acetaminophen).
       Statin drug to lower cholesterol reduces breast cancer risk.
       Taking estrogens and/or progestins increases breast cancer risk and speeds the cancer appearance and increases and worsens chance of cure. This includes hormones to treat menopause, to treat vaginal bleeding and for birth control. Because these hormones, carefully used, may have benefits, one should balance benefit against risk and if you choose to use, do lowest doses and take precautions for early detection and prevention.
       The anti estrogens Tamoxifen or Raloxifene taken daily for years in high-risk patients reduce breast cancer risk but at cost of increased risks for uterine cancer and pulmonary embolus and menopause symptoms (But Tamoxifen or Raloxifene protects against osteoporosis.) It is not for the average case but may be considered for one who knows she is very high risk - like a genetic condition, or like the already treated breast cancer to prevent or slow the time to recurrence of the old cancer or development of a new cancer in opposite breast. Women who no longer have uterus do not need to worry about uterine cancer, so for them preventive Tamoxifen is much less problematic. Alternatively, removal of all normal breast by simple mastectomy on both sides is preventive in high risk.
       Androgen steroids promote breast cancer so do not use them, as some do, for sports or to increase sexuality after menopause.
       Healthy eating for cardiovascular reasons also lowers risk for breast cancer. So eat healthy - low red meat, high vegetables and fruits, low kilocalorie meals. And keep BMI below 25.
       Ethyl alcohol ups risk for breast cancer. If you choose to drink alcohol, use wine or beer, or dilute hi-proof drinks 50:50 with water.
       Once you have set this advice in your mind, try to live a happy non neurotic life not obsessed by breast cancer, but self examine your breasts monthly at start day of menses cycle and from age 40 do screening mammography.
       Genetic causes are 1% of all breast cancer. The famous gene is BRCA whose testing is possible. The gene alone gives a high risk for both breast and ovarian cancer but the risk for breast cancer alone fluctuates with other genetic and environmental factors so do not get any breast removal based purely on BRCA. A high risk with BRCA is best dealt with by careful surveillance and after childbearing is complete, to take tamoxifen one a day for life and a hysterectomy and bilateral salpingo-oophorectomy with menopause. Suspect if your mother and/or sisters or children have breast and/or ovary cancers. If they do, be sure to follow the advice here but do not get neurotic over it.

      The future of breast cancer treatment is gene array testing of each cancer for its susceptibility to each adjuvant drug - so called targeted therapy in 2020 becoming available at top centers.


     END OF CHAPTER. To read next click 10-17 Leukemia - Living Life on Your Feet Not on Y...








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