Mammogram Screening & the Struggle to “Do No Harm”

The Uncertain Benefits and Clear Harms of Routine Mammography

I’m back with provocative thoughts on science.  While I believe science can be used for good, I worry that much “science” fails to discern truth from bias. I can testify that physicians often struggle to tell the difference.  And this seems clear in the field of preventive medicine.  Today, I’ll explore the myths and controversies of screening mammograms.  

I’ve done my best to objectively portray what is known and unknown in this space. Yet, so much more could be said.

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Ms. N is a 70-year-old woman I see regularly for well-controlled diabetes. Recently, she called my office with a new complaint: breast pain and nipple retraction. I ordered a mammogram to visualize the breast tissue via x-ray. It showed calcifications suspicious of breast cancer. A subsequent biopsy confirmed the diagnosis. 

I called to tell her the result.  She was stoic, not revealing a hint of shock or devastation. She simply asked, “What do we do next?” Last week, I saw her in my clinic. We discussed the good news. It seemed unlikely that the cancer had metastasized. Her oncologist reported a high likelihood of remission after treatment. Nevertheless, she confided in me that she found it difficult to sleep, given recurrent spinning thoughts.

Because Ms. N called right away, the initial diagnostic mammogram was helpful.  It started a cascade of testing and treatment needed to eliminate the cancer.

While diagnostic mammograms more often lead to life-saving or life-prolonging treatment, this is not the focus of my essay today. Instead, I will focus on the ambiguity of screening mammography.  This is when a person pursues mammography in search of “early” breast cancer in the absence of symptoms.

Several years ago, I offered screening mammograms to Ms. N, but she declined. I didn’t belabor the subject. The decision was hers to make. But in retrospect, catching the cancer earlier wouldn’t have meaningfully changed her prognosis.

In primary care, it is generally believed that the detection of “early” cancer saves lives. This belief is systematically enforced through medical education. To doubt this belief is frowned upon. And underappreciated is that mammogram screening can lead to significant harm. The cumulative harms might outweigh any benefit. 

After digging into mammography history and research, I am left with more questions than answers. How did general practitioners develop such dogmatic beliefs in the absence of positive quality research? How can patients navigate a medical system where physician biases contradict patient autonomy? Can physicians abandon harmful beliefs? Or is it too late?

The Dawn of Mammography

I admire certain public health efforts.  As I’ve mentioned before, a hero of mine was once arrested for defacing cigarette ads.  This effort was honorable. Physicians have a duty to inform the public of potential dangers. Lately, I see more dangers emerging from our own healthcare system. In my line of work, I see harm being done in the field of preventive medicine. Specifically, I worry about certain public health interventions that target healthy people.

I'm obsessed with randomized controlled trials (RCTs). When designed well, RCTs are the gold standard for unveiling a medical intervention's benefit. Participants are randomly assigned to either an experimental intervention or placebo. Despite the simple design, the idea was only conceived in 1948! The delayed emergence of RCTs in human history is baffling. For reference, the theory of relativity and quantum theory were both conceptualized at the turn of the 20th century.  X-ray machines were invented in 1895.  

The first and only United States RCT on mammogram screening started in 1963. The trial found that a combination of breast exams and mammogram screening after 50 years of age was associated with a 30% decrease in breast cancer mortality. But the trial had a major flaw. Researchers discovered that some participants were previously diagnosed with breast cancer. These individuals were removed from both the control and intervention arms of the trial.  However, the removal of patients was likely done unevenly. A slight bias in choosing which patients to eliminate likely overstated the benefit of mammography. (Mukherjee, pg 297)

Yet, the American Cancer Society (ACS) didn’t miss a beat. They started a mammography “demonstration” involving 250,000 women. The ACS believed no further research was needed to push for nation-wide mammography. Perhaps they still believe this to be true. 60 years have passed since this first RCT.  And no repeat RCT has been attempted again the the United States.

With mammography fervor on the rise, other countries attempted their own trials. In 1976, Sweden came to the rescue with an RCT in the city of Malmö.  Even the harshest critics admit the quality of the Malmö trial was “medium”. The trial did not find any benefit among women between 45-75 years old.  But specifically among individuals ages 50-75, mammogram screening appeared to decrease the risk of breast cancer mortality.  

The United States and Malmö trials laid a foundation for widespread advocacy in favor of mammograms. While some skepticism existed in niche circles, enthusiasm persisted and snowballed for half a century.

Indoctrination

In medical school, memorization and regurgitation are tickets to graduation. I personally used a collection of ~30,000 flashcards.  It was a powerful feedback loop: the more I was rewarded for memorization, the more I believed that (1) there's overwhelming consensus in the medical field and (2) memorized “facts” were not up for debate. Survival required keeping my head down. During medical school, we only had a few poorly attended lectures on how bias manifests in research and medical practice.  Critical thinking in this domain is not tested thoroughly on board examinations, so most medical students focus their attention elsewhere.

Even during residency, I find scant opportunities for leisurely discourse on ambiguous topics. I find myself writing this post at 1 a.m. on a weeknight. 

An Anki flashcard memorized by thousands of US medical students.

During residency, red flags piqued my interest in mammography. The demand that I collect mammograms was incessant and enthusiastic. Conversations on the topic lack elaboration on the harms and benefits of screening. In the past 4 months, I've attended four educational activities where my duty to collect as many mammograms as possible was emphasized. Without fail, one outcome of mammogram screening was always mentioned: clinics get reimbursement for ordering them. Multiple times, I’ve heard it stated explicitly that the financial well-being of clinics depends upon physicians ordering mammograms.

The language used to talk about patients feels uncomfortably antagonistic. The goal is for patients to “comply” to mammography. Never is it suggested that a patient's well-informed decision should be respected. There is only one acceptable outcome.

Doing Harm

Not all breast cancer is equal.  Some is tragically aggressive and fatal.  But sometimes, it never threatens a person’s life. Autopsy studies show that an astounding number of people live with cancer that never becomes fatal. It is even possible for cancer to regress spontaneously. Finding and treating cancer that never would have caused harm is called overdiagnosis.  

And this is how screening mammograms can cause harm.  If mammogram screening finds a cancer, it may be treated more aggressively than is necessary. What is necessary cannot be determined. This means that some people undergo unnecessary biopsies, chemotherapy, and disfiguring surgeries. How often does this happen? I’m glad you asked. Overdiagnosed by Gilbert Welch makes the harms of overdiagnosis easy for physicians and patients to understand. On page 149, he summarizes the harms and benefits of mammography screening:

I recently lamented to a family member my concern about harms caused by mammography. Her response was, “What harm?!” She is far from alone in responding this way. A 2000 US survey found that only 8% of women were aware that breast cancer screening can cause harm. Who is responsible for this tragedy? A 2011 survey casts the blame: 90% of physicians mention mammogram screening benefits while only 19% mention harms. Currently, 76% of women aged 50-74 in the United States receive regular mammography screening.  But if physicians properly disclosed the harms how many women would actually consent to this testing?

While the above table is helpful, I worry that even this perspective misses the forest for the trees.

Does Mammogram Screening Even… Save Lives?

Since the 1970s, many more RCTs have been conducted. And the field of oncology has advanced drastically.  We are much better at treating breast cancer. We are more conservative and precise with surgical intervention. Given the medical field is constantly changing, we must also constantly reassess the need for mammogram screening.  Fortunately, newer mammography data exists, though much of it is flawed. One meta-analysis attempts to separate adequately and inadequately randomized trials.  Among the adequately randomized trials, mammography screening led to a statistically significant decrease in breast cancer deaths.  However, the benefit is modest compared to the trials with poor randomization.

But here is the kicker: aggregated data in this meta analysis didn’t show that mammography screening increased or decreased all-cause mortality.

In other words, while screening may prevent some breast cancer deaths, it seemingly does not lower overall mortality. Perhaps the cumulative harms negate the benefit.

Fast forward to 2023. The United States Preventive Service Taskforce (USPSTF) imminently plans to recommend mammogram screening starting at 40 years old. Does USPSTF properly weigh research quality when making screening recommendations, considering potential harms from overdiagnosis? I worry they do not. I also worry about patients who see doctors that accept USPSTF recommendations without critical evaluation.

Scientists desperately need to ask and study this painfully simple question: “Does mammogram screening save lives?”

We must not miss the forest for the trees.

The Struggle to “Do No Harm”

Physicians are primed to cause harm when it comes to mammogram screening. They are inadequately educated on this topic and financial incentives compromise patient-physician relationships across the United States.

Vinay Prasad urges physicians to not take the USPSTF’s mammography recommendations at face value. Not every “A” or “B” recommendation is in a patient’s best interest. Healthcare systems should not track or pressure physicians to collect mammograms. We must counsel patients on what is known and unknown, then respect their well-informed decisions.

Most physicians do not disclose the harms of mammography screening and only mention exaggerated benefits.

The United States healthcare system seems intent upon me harming and disrespecting patients. I struggle to see how I can responsibly navigate this system. But I am trying to figure out how to do better.

I would love to hear your thoughts.

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This article was largely inspired by this talk by Vinay Prasad. He led me to many fascinating articles, Mammography Screening: Truth, Lies and Controversy by Peter Gøtzsche, and Overdiagnosed by Gilbert Welch. All incredible resources.