**7. Contrast-Enhanced Mammography**

The ability of contrast to detect cancers in dense breast tissue on mammograms is now well established with contrast-enhanced breast MRI and contrast-enhanced mammography (CEM). However, it is well recognized that many benign breast lesions will also enhance with contrast. In this special Issue, Fusco et al. performed a study to discriminate between benign and malignant breast lesions with radiomic metrics extracted from CEM and DCE-MRI images [12]. A total of 79 pathologically proven breast lesions (48 malignant and 31 benign lesions) in 54 patients were studied. Various features on both modalities were studied, with the two best predictors found with an Area Under the Curve (AUC) of 0.71 on the mediolateral oblique (MLO) image of CEM. When all 18 features derived from MRI and CEM were combined, the AUC reached 0.88. The use of morphological assessment was insufficient while the radiomic features allowed for a better discrimination of benign- from malignant-enhancing breast lesions. In another study of CEM, Steinhof-Radwanska et al. [13] studied its use on patients with breast cancer treated with neoadjuvant chemotherapy. In their retrospective study of 63 patients with breast cancer who underwent CEM to assess their chemotherapy response, they found that CEM was highly sensitive in detecting a complete response to chemotherapy (85.7%), but it tended to underestimate the correct tumor dimensions. Recognizing this morphological limitation, CEM is a viable alternative to contrast-enhanced MRIand is effective in the detection of a complete response to chemotherapy.

## **8. Dense Breast Tissue**

In a comprehensive review, Gordon [14] summarizes the impact of dense breasts and the stage of breast cancer at diagnosis. In it, she cites the relative loss of breast cancer mortality reduction in screened women with dense compared with non-dense breasts (13% vs. 41%), and the increased breast cancer mortality relative risk of 1.91 in women with dense breasts. The various supplemental screening modalities are discussed, including those with the greatest ability to reduce the inequity of screening for breast cancer in dense breasts, and the balance of risks and benefits of each one.

In the study by Hadadi et al. [15] of 534 Australian women recalled from screening with mammographic abnormalities and subsequent digital breast tomosynthesis (DBT) and breast ultrasound, breast tissue density was found to correlate significantly with recall rates. Mammographic abnormalities were more likely to be recalled in women with dense breasts. Breast ultrasound was shown in this study to be more useful than DBT at reducing the rate of unnecessary breast benign biopsies.

#### **9. Harms of Not Screening**

The harms and benefits of screening mammography are not fully understood by many oncologists and physicians. World expert, Harvard Professor Kopans review, named, "Misinformation and Facts about Breast Cancer Screening", listed the 10 reasons that screening mammography is effective at saving lives from breast cancer by 40% or more [16]. Citing widely from the literature, he uncovers the myths that prevent women in their 40s from routinely being included in screening mammography programs. He summarizes the 1980 Canadian Breast Cancer Screening Studies' (CNBSS) significant flaws that include the subversion of the randomization allocation, poor image quality of the mammography, the inclusion of many symptomatic women and allocation of more to the so-called "screening" arm, and shows why the CNBSS are not credible to determine screening policies.

A review by Appavoo illustrates the influence of the CNBSS on national and international breast cancer screening guidelines [17]. She provides insight into how the flawed studies came to be included in reviews that inform guideline processes. Illustrating the lack of expertise in healthcare guideline processes and drawing on examples of epistemic trespassing, manufactured doubt, and the misuse of the evidence-based review principles, she lists many reasons for the ongoing inclusion of CNBSS in the body of mammography screening evidence. She suggests reforms for the creation of new breast cancer screening guidelines that include expert knowledge and sensitivity to context and the need for fundamental change.

In the last but potentially most clinically relevant article, Dale, Tomaso and Gay summarize the lived experiences of many patients with breast cancer, many of whom were impacted by outdated screening practices [18]. Told through eight stories of women personally affected by breast cancer, the authors depict variable screening practices across Canada for women in their 40s, contrasting the early stage of breast cancer in two different 40 year old women who were both detected by screening mammography in the provinces of British Columbia and Prince Edward island, while another woman in Alberta presented with stage IV breast cancer two years after being dismissed by her family physician when she requested to be screened with mammography, citing guidelines that she was too young. The healthcare costs and emotional and physical toll on women diagnosed at a later stage highlight the harms of not screening women for breast cancer. The authors call on the medical community to do everything possible to reduce advanced stage breast cancers by harmonizing and optimizing screening practices.
