BREAST CANCER MAMMOGRAPHY - WHY THE CHAOS?

Women have to be confused with the plethora of papers that seem to question the value of mammography as a screening technique in symptomless patients and those not at increased risk for breast malignancy. While there seems to be very little controversy over the management of clinically detected breast cancers there is a continuos swirling debate around preventative mammograms that gets more and more intense every day. Ductal Carcinoma in Situ, (DCIS), where the cancer cells are limited to the breast ducts and not in the breast tissue, and which entity is predominantly diagnosed by mammography, is the most recent breast disease to have its management strongly challenged. How can this all be? Surely scientific medicine has certainty?

HOW DO DOCTORS DECIDE TREATMENT?

To understand it all one has to analyze how medical knowledge is obtained and how the discipline of medicine decides on treatment options. Some therapeutic choices in the not so distant past such as blood letting and leeches were based on belief and nothing else. One would dearly like to believe that medicine has progressed beyond that, which it has, but it has not nearly the scientific precision that some of its practitioners pretend it has. The dream that Flexner had when he revolutionized the study, practice and education of medicine has not fully materialized. His report, which had the imprimatur of the American Medical Association, was published at the turn of the twentieth century and had as its objective to make medicine a purely scientific discipline. To effect this he had the medical schools that had no scientific emphasis to medicine shut down. The reformer never took into account the variables of doctor and patient that go into defining disease and its management. 

EMPIRICAL DIAGNOSES

So to return to what predicates medical decisions. A large number of treatments, especially surgical, are pragmatic and commonsense. These are deemed to be empirical and have not been subject to rigorous scientific assessment. For example, the field surgeons in war learned pretty fast if you didn’t amputate a highly compromised limb, gangrene would set in and result in death. So that is what they did with no scientific trials to prove them right. That principle holds to this day although with modern medicine and anesthesia one can battle more successfully to save many limbs. Likewise surgeons did not have to stand around and watch too many appendices burst with subsequent death to realize that removal of the appendix was the way to go with symptoms and signs of that condition. 

Other medical disciplines also got the message through observation or obvious commonsense. Anesthesiologists didn’t need too much cajoling to use chloroform as opposed to alcohol and holding the patient down in surgery. The penny dropped in obstetrics when they finally put two and two together noting that puerperal sepsis was occurring in mothers that delivered in the hospitals and not in the community. Semellweis who made this observation linked it to hand washing. He was spurned by his colleagues as he had no scientific basis for his theory but he was proved right. 

But not all instances of empirical, intuitive and commonsense approaches turn out to be correct.

LIMITATION OF INTUITION, COMMONSENSE AND EMPIRICAL MANAGMENT IN TREATMENT SELECTION.

Two examples where practical commonsense and intuition have failed dramatically in management options relate to the prevention of coronary heart disease. Working on the assumption that women do not suffer from Coronary Heart Disease till their menopause men were given female hormones as a prophylaxis with disastrous results. Likewise it was the conventional wisdom that females after menopause should be put on supplemental hormonal therapy as they would be cardiac protective and decrease cancers. After years of comparative research studies the consensus was that coronary artery heart disease, breast cancer, stokes and thrombotic events were all increased. So intuition and logic is not enough to advocate a medical treatment. 

So we see that empirical treatment plays a big role in medical management. However except in obvious situations the empirical hypothesis needs scientific evaluation otherwise the outcome cannot only be of not be any use it can do harm.

The two commonest ways to scientifically evaluate an empirical management or any hypothesis for that matter is either by an observational trial to see outcome of treatment over a long period of time or a comparative study to compare the new management with either nothing or another established approach. There are several variations to these two types of research and this is not the place to discuss them other than to state that the more rigorous the study is the more reliable the result. 

THE ROLE OF MAMMOGRAPHY IN THE PREVENTION OF BREAST CANCER AND HOW WE GOT THERE.

Let us look at the current controversies on breast cancer management and see how we got there. Breast cancer is the commonest female cancer occurring in one in eight women during their life time with over two hundred and thirty thousand women diagnosed each year. Even today empirical intuitive treatment still plays a major role in management decisions and this to a certain extent has created the dilemma that has occurred in the recommendations for mammogram screening and treatment of DCIS. 

Introduction of Mammography.

Mammography is a relatively new concept that was introduced in the 1960’s. It was based on the logical assumption that if one was able to diagnose breast cancer, early, before it became clinically evident, then one would be able to treat it earlier and thereby prevent the spread of the cancer and therefore death. The introduction of routine screening of women throughout the world has been tremendously successful with in some areas nearly an eighty percent success rate. This tour de force has coincided with the introduction of more and more sophisticated and powerful mammography of the breast tissue. Like so many medical interventions the compelling nature of the rationale of the approach resulted in wholesale adoption before scientific evaluation had taken place. Not only was the actual concept not assayed neither was the sophisticated technology, with the latest being the 3 - D mammogram, evaluated as to its impact on the disease. The more sophisticated the screening technique the higher the detection rate of cancer or DCIS.

Evaluation of  Screening Mammography.

The impact and outcome of mammography screening has now been extensively and scientifically evaluated. The results have been to put it kindly, disappointing. The number of breast cancers diagnosed have increased but the number of deaths from the disease have almost remained constant. The Cochrane Collaborative Group, which is the most prestigious group for evidence based medicine maintains that there is no quality evidence that mammography has decreased the death rate from breast cancer. They have taken their argument one step further and maintained that it is uncertain whether the screening does more good then harm.

Four types of cancer types have been recognized:

1. Slow growing so even if detected late does not impact outcome.
2. Fast growing so that even if detected early it cannot influence outcome.
3. Cancers that are so slow growing that should be left as patients will die with them.
4. A small number of cancers detected that benefit from earlier detection and treatment. 

It appears that there is a positive impact of screening mammography in the age group of women between 50 and 74 years of age where cancers are detected that will benefit by early treatment.  In a review article in Medscape in 2009 it was cited that mammograms in the age group between 50 to 74 would save 1.8 lives of a 1000 women screened over a period of 15 years. The Canadian Task Force had similar results starting that screening 720 women for 11 years would prevent 1 breast cancer. 

That respected Cochrane research group stated that if screening mammography started at 40 years of age, 50,000 women would need mammography over 15 years to save one life at an additional projected financial cost of $6.5 billion. 

Risks of Mammography Screening

Assuming the Cochrane group is more or less on the money and cost isn’t taken into consideration, why wouldn’t society want to save one life in 50,000 screened over more than a decade? It boils down to the risks. David Newman in his book “Hippocrates Shadow” argued that, on balance, the mass screening produces cancer phobia and unnecessary surgery and treatment. The anxiety and even panic that mass screening produces is immeasurable but a constant as any practitioner will relate. However there are a number of measurable side effects such as false positives, over diagnosis and radiation.

1. Over diagnosis is rated as the biggest hazard of mass screening. In effect this relates to operating on patients that do not need surgery. The number in this category varies according to the study but in 2012 the UK Cancer Research Group stated that 1 in 5 breast cancer cases were over diagnosed. A much higher figure, one in three, was quoted in s study published in the British Medical Journal in 2009. Analysis was from several countries including the UK, Canada, Australia and Sweden. The American Cancer Society rates the figure between 0% to 30%.
2. False positive results occur when the initial mammography screening results indicate a cancer and further tests such as a biopsy prove them wrong. According to the American Cancer Society that of the ten percent of women who are diagnosed as positive on mammography a half to three quarters have not got the condition on further testing. This results in unnecessary anxiety and expense all over the whole board. 

3. Radiation is really a big cancer risk in the younger patients. Above 50 years it is minuscule. 

MAMMOGRAPHY SCREENING AT THE END OF THE DAY

There appears to be a consensus that mammography is most cost effective when performed every second year in women between ages 50 to 74. The US Preventive Services Task Force, (USPSTF), are in line with this approach but this is such a hot political potato that Congress overrode their 2009 recommendation insisting that insurance companies pay for annual screenings from forty till death. As a public health economic issue the cost with 70% of eligible women participating is $7.8 billion per year. If the target 85% screening rate would have been achieved the tab would have been $10.1 billion. (Annals of Internal Medicine 02/04/14).

Several studies lead the USPSTF in 2009 to change their recommendation as to who  should be screened and how often. Their principal recommendation was for screening for women between ages 50 to 74 every second year. This would bring down the cost to $3.5 billion a year. Bearing in mind that 50,000 women over 40 years of age screened annually will save one life but leave in its wake all the morbidity and even possible mortality that are adverse effects of the screening must surely make the medical world and the Public Health authorities relook at the current strategy of routine annual screening of all women over 40 years of age.The additional cost of including the 40 to 50 year old sector is $6.5 billion.

MAMMOGRAPHY’S DISEASE - DUCTAL CARCINOMA IN SITU. (DCIS)

With the introduction of routine mammography screening a new disease DCIS was defined. The latter rarely presented as a clinical entity. Put another way, in by far the majority of cases there is no mass in the breast, no nipple discharge or skin changes so without routine mammography the diagnosis of DCIS would not have been made. The irresistible inference was that DCIS, where the cancer cells are just in the ducts and not in the breast tissue, was the precursor to invasive carcinoma. With more and more sophisticated technology being developed the diagnosis was made more and more often. About 60,000 cases were diagnosed in 2014. The treatment of DCIS is essentially the same is Stage 1 invasive carcinoma. That includes lumpectomy, (removal of the area where DCIS is with wide margins), mastectomy, radiotherapy with or without lumpectomy or unilateral or bilateral mastectomy. This is pretty radical treatment to institute on the basis of “intuition”.  

Now the radiologists make this diagnosis on the basis usually of patterns of calcification. As there is no mass in the breast the most efficient way to do the biopsy to confirm DCIS is by stereotactic core needle biopsy. The latter uses x-ray equipment and a computer to analyze pictures of the breast. The computer then pinpoints exactly where in the abnormal area the needle tip needs to go - a complex and costly procedure. Up to three quarters of biopsies are negative.

MAIN FINDINGS OF RECENT DCIS STUDY.

With the scientific studies now emerging the intuition on DCIS has been challenged in a number of areas. A major study published in the Oncology Journal of the American Medical Association involved the follow up of over a 108,000 women who had been diagnosed and treated for DCIS. The follow up was for 10 to 20 years and yielded many important findings: (Whether these will change doctor or patient behavior is another matter). 

1. Regardless of the management of DCIS, which ranged from bilateral mastectomy to simple lumpectomy with or without the radiation, the outcome was the same.

2. While the risk of death from breast cancer was higher in the DCIS group the significant predictors of mortality were women under the age of thirty five and black ethnicity. The women under thirty five were obviously not diagnosed by screening and must have had clinical indications for the mammogram. The risk of dying was greater at a young age being 17 times greater in women under 35 as compared to 1.4 in those over 65.

3. Prevention of invasive carcinoma in the breast with treatment did not prevent death from breast cancer. However the deaths were due “secondaries” just as if these DCIS were invasive carcinomas to begin with.

DILEMNA ON DCIS

This paper has evoked responses across the board ranging from DCIS must be treated like Stage 1 invasive breast carcinoma, (which for practical purposes it currently is), to it should not be treated at all and just watched with repeated mammograms. Bearing in mind that DCIS has the same prognosis and natural history as invasive carcinoma and treatment of DCIS did not prevent the latter there is a strong argument for the wait and watch approach till if and when the invasive carcinoma presents. This would prevent the vast majority of DCIS patients being treated unnecessarily. Close on sixty thousand women are diagnosed with DCIS and the majority could be being over-treated, at great cost with endless morbidity, as a result. It is apparent as well that there a subgroups with DCIS that must be at more risk than others and while age and ethnicity have been identified studies of those with hereditary predisposition, estrogen receptors status and histology for example need to be evaluated. Surely all workers must agree if this group is to be treated that all radical treatments must be out.

AT THE END OF THE DAY

* The death rate from breast cancer has remained virtually static for decades. What improvement there has been is generally accepted to coincide with a decrease in hormone replacement therapy which had been shown to be a cause of breast cancer. It is thus obvious that all this activity needs a dispassionate review and scientific assessment rather than continuing these visceral judgements in the management and screening of breast cancer.  Society has to decide whether they wish to modify the criteria for these costly and radical treatments that show little benefit and high adverse effects. 

* The problem is that standing in the way of the rethink is doctor and patient behavior - two variables that are never taken into account yet it is doctor bias that has got into this mess in the first place. The medical profession now sanctimoniously argues that the pros and cons of treatment should be discussed with the patient so they can make an informed choice in situations they probably would not have been in if there had been the appropriate studies in the first place. On the other hand patients don’t see the necessity of scientific studies either if they are persuaded by the “logic” of the treatment. When, in 2009, the USPSTF made its recommended changes for routine mammogram screening at the age of 50 years there was an outcry second to none. The US Congress had to step in and decree that medical insurance companies regard 40 years as the age that would recognize and pay for.  Society swallows buckets of pills, with only anecdotal evidence of efficacy, that they intuitively believe will help. Recently pressure groups even influenced the FDA, society’s gatekeeper to keep science in medicine, to reverse their decision to register a medicine that supposedly increases a female’s libido. In studies the medicine has shown doubtful effectiveness coupled with unacceptable side effects and its registration had twice been denied by the FDA. 

* Costs do matter. If one recognizes that Planned Parenthood that performs over 10 million women services per year do so at a  cost of about $200,000,000 then $6.5 billion is a lot of money. They perform 10 million services and a million of those are for breast and cervical cancer testing that otherwise would not be done. They diagnosed 85,000 cancers, provided 4 million birth control encounters and 2 and a half million sexually transmitted screenings or treatments.

* As far as mammograms are concerned the US Preventive Services Task Force’s recommendations on mammography which include routine screening of symptomless between 50 and 70 years of age should be reconsidered. With regard to DCIS found on screening a study needs to be designed to evaluate the difference between watchful waiting with repeated mammograms versus lumpectomy versus lumpectomy and radiation. 

To quote Dianne Rehm on her influential Public Radio morning show, where she was trying to make head or tail of the experts’ opinions on the recent DCIS study, that should she be diagnosed with the DCIS at this stage of her life she would do nothing.