Randomized Controlled Mammography Screening Trials Revisited

In this issue of the Journal of Breast Imaging, the validity of the Canadian National Breast Screening Studies (CNBSS) is deeply questioned (1,2). Of the eight randomized controlled trials (RCTs), only the two CNBSS studies showed a negative impact with screening mammography (3,4). In our Science of Screening article, Seely et al (1) detail the many ways that the CNBSS studies fail to meet accepted standards of RCTs, including inadequate power to detect significant differences in breast cancer mortality; poor-quality mammography even for that era; inclusion of women with symptoms of breast cancer; and a study design that allowed for misallocation to the screening arm at randomization. These points alone should prompt reconsideration of whether these studies should be included in decision making about screening mammography guidelines.

A recent eyewitness account of tampering with the randomization process—research coordinators skipped lines on a paper randomization form to prioritize patients with suspicious clinical findings to undergo screening mammography (5)—supports the long-held hypothesis that flaws in the process were to blame for the disproportionate number of women with advanced breast cancers being assigned to the screening arm of the trial (1). In fact, almost 80% of the most advanced breast cancers (at least four positive axillary lymph nodes) were assigned to the screening group (6). In discussion with the lead author, Jean Seely, University of Ottawa, this eyewitness account prompted her and her coauthors to perform an original research study in which they identified research staff who participated in the CNBSS studies and performed standardized interviews (2). They interviewed 29 surviving members who were radiologists, nurses, radiology technologists, or other research staff in either the CNBSS-1 or CNBSS-2. They found that 41% of staff (12/29) confirm that women with symptoms of breast cancer were systematically recruited to the study at some sites. More than half (55%, 16/29) confirmed that training in screening (performing or interpreting mammograms) was very limited and resulted in poor image quality (14/29, 48%). In addition, 27% (8/29) report that at some sites, surgeons did not follow through on radiologists’ recommendations to biopsy patients with suspicious mammographic findings unless there was a corresponding clinical finding.

An accompanying editorial by Stephen Duffy (7) calls the Yaffe et al article (5) “a bombshell,” particularly noting the eyewitness account of a clear protocol violation of the randomization process. The other eyewitness accounts (2) further expand and support the deep deficiencies of the CNBSS, including active recruitment of symptomatic women to a screening trial—long suspected but now supported. Dr Duffy further notes that a very important point of the Science of Screening article by Seely et al (1) is that the differential in allocation of women with advanced cancers to the screening arm was previously defended by others because the breast cancer risk factors were similar between study arms. Duffy (7) goes on to state, “Both (Seely et al) papers (1,2) conclude that CNBSS can no longer be considered safe to include as evidence to inform screening policy. Sadly, this reader can only come to the same conclusion.”

Given this overwhelming documentation (1,2) of poor study design, inclusion of symptomatic women in the study, a clear protocol violation of the randomization process, and poor imaging and training of those acquiring and interpreting mammograms, the time has come for those in decision-making positions to disregard the CNBSS results. Some may even propose that the articles related to the CNBSS be redacted entirely.

It is interesting and surprising that the CNBSS results and other RCTs are used to inform current policies regarding screening given that they were performed more than 40 years ago. I suspect few JBI readers would have been in practice at that time. Technology has changed remarkably during these decades, with likely none of us currently using the film-screen mammography used for the RCTs and most using digital breast tomosynthesis (DBT) as well as other screening modalities of US and MRI. Our Scientific Review article by Chikarmane et al (8) in this issue of the JBI addresses a new challenge with advancing technology that discusses the benefits and challenges of using synthetic 2D mammography over combined 2D + DBT. The contrast of this article to the RCTs of four decades ago emphasizes how far we have come in the detection of breast cancer with mammography.

We have several original research articles that are surveys from the members of the Society of Breast Imaging (SBI). In the first article, Milch et al (9) surveyed SBI members regarding communicating with patients during the COVID pandemic and found that nearly half of those responding to the survey (46%) reported a diminished ability to fulfill patients’ emotional needs, which was associated with younger age, higher anxiety, and higher psychological distress of the radiologist. The second survey article by Donchos et al (10) found that 69% of respondents provide reading of outside studies, nearly all (96%) with the indication of second opinion for biopsy recommendation. Physician time was the most commonly cited barrier to providing this service. A survey study of SBI members by Weinfurtner et al (11) found strong interest in mentorship (65% of respondents). Interest in mentorship was most common for those who were younger, female, identified as underrepresented minority, in academic practice, and fellowship-trained. These results suggest that there are significant opportunities for supporting radiologists through a mentorship program, which the SBI is actively developing. An additional original research article by Murakami et al (12) furthers our ability to use quantitate parameters at MRI to predict pathologic compete response.

In an earlier survey of SBI members, Parikh et al (13) found that interactions with difficult administrators were a significant cause of stress for half of the respondents. In this issue of JBI, a very practical article by Wahab et al (14) reviews how to “manage up” by developing relationships with practice administrators. The article beautifully discusses different workplace leadership styles that are important to understand about those above you as well as yourself. The article then discusses how to develop effective communication styles and strategies. As written, it is breast imaging–specific, but I suspect many of our colleagues in other subspecialities will also benefit from review of this article. The second Clinical Practice article is also related to communication and relationships in the management of challenging patient interactions by Soo et al (15). Although many radiologists shy away from challenging patient interactions, developing an approach to managing these patients benefits patient care.

Our Training and Early Career article by Monga et al (16) reviews strategies to recruit and retain a diverse workforce in breast imaging that includes mentorship and sponsorship, fostering an inclusive environment, and purposefully retaining and promoting a diverse workforce.

I found the Educational Review article on autologous fat grafting by Winkler et al (17) fascinating. It is not commonly performed where I practice, so I have had little exposure to this topic. Very educational. Likewise, the Radiologic-Pathology article on angiolipomas (18), a rare benign tumor that can be difficult for pathologists to distinguish from angiosarcoma, has beautiful imaging correlation and was also very educational. And, finally, our unknown case and image spotlight cases are fascinating (19–21). I won’t spoil them for you.

This issue of JBI contrasts the frustration with public agencies that use outdated and poorly performed RCTs to our rapidly advancing field using synthetic 2D mammography with DBT and quantitative MRI parameters to predict pathologic complete response to neoadjuvant chemotherapy. The issue brings hope that the CNBSS studies will be disregarded in making policies regarding screening mammography because of violations of accepted RCT standards, but also hope in developing technology that will continue to improve patient care over the subsequent decades.

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