**1. Introduction**

Breast cancer affects too many of us. The preventable loss of life of mothers, sisters, daughters, grandmothers, fathers and beloved friends must be addressed through science. Female breast cancer has now surpassed lung cancer as the most diagnosed cancer in the world [1]. Almost 2.3 million new cases were diagnosed in women in 2020 [1]. Survival from breast cancer has steadily increased, and in Canada, breast cancer mortality has decreased by 46% since its peak in 1986, where the age-standardized mortality rate fell from 42.7 deaths per 100,000 to a projected rate of 23.1 deaths per 100,000 in 2021 [2]. While 65% of women with breast cancer are diagnosed at early stage I or stage II (localized), there are still far too many women who present at a stage III (regional) (27%) or stage IV (de novo metastatic disease) (6%) [3]. These proportions vary according to race and ethnicity [3]. Unfortunately, the early-stage diagnosis of breast cancer still progresses to metastatic breast cancer in 20–30% of women [4]. Improved survival has been achieved through the early diagnosis of breast cancer with screening and more effective and targeted treatments. Significant gaps remain, however, where an early diagnosis of breast cancer in certain populations is not achieved, including women with dense breasts, those of Black, Asian, Indigenous, and Hispanic ethnicities, and in women aged 40–49 years who are not routinely included in screening mammography programs. In addition, women at high risk who are 30 years and older and men may not be detected at an early stage. In this Special Issue of *Current Oncology on Breast Cancer Imaging and Therapy*, the latest evidence is presented on the early detection of breast cancer and treatment of breast cancer, highlighting the areas where this may be improved.

#### **2. Adjuvant Endocrine Therapy for Breast Cancer**

1

Rosso et al. evaluated the importance of adjuvant endocrine therapy for hormonereceptor-positive breast cancer in a retrospective observational study of 373 women with breast cancer [5]. In this survey study of 64% postmenopausal women, 84% experienced side effects, the most common being arthralgia, hot flushes and vaginal dryness. Significantly higher rates of side effects were found among women who also received adjuvant chemotherapy compared with those who did not (84.8% vs. 78.6%; *p* < 0.001). Premenopausal women were also more likely to experience side effects than postmenopausal women (92% vs. 75%; *p* < 0.001). In their study, 12% of patients stopped the adjuvant endocrine therapy mostly due to the side effects; those who did discontinue treatment more often reported severe side effects compared to those who did not (44% vs. 15%; *p* < 0.0001).

#### **3. Men and Breast Cancer**

Appiah et al. reported a prospective study of breast cancer among men in the United States; the research investigated 5216 men with breast cancer aged ≥40 years from the Surveillance, Epidemiology, and End Results program from 2000–2019, and studied the relation between breast cancer treatment and cardiovascular disease mortality [6]. They investigated the impact of race/ethnicity. After a median follow-up of 5.6 years, 37%

**Citation:** Seely, J.M. Progress and Remaining Gaps in the Early Detection and Treatment of Breast Cancer. *Curr. Oncol.* **2023**, *30*, 3201–3205. https://doi.org/10.3390/ curroncol30030242

Received: 26 February 2023 Accepted: 3 March 2023 Published: 8 March2023

**Copyright:** © 2023 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

(1914) of deaths occurred, of which 25% were attributable to cardiovascular disease and 35% to breast cancer. In multivariable analysis, men who received chemotherapy had a significantly elevated risk for cardiovascular-related death (HR: 1.55, 95% CI: 1.18–2.04). There was a significant interaction between race and ethnicity and cancer treatment on the risk of cardiovascular-disease-related mortality (*p* = 0.005), with higher levels among Hispanic (HR: 3.96, 95% CI: 1.31–12.02) than Black and White men.

#### **4. High Risk and Breast Tissue Density**

Rusnak et al. performed a prospective study of 139 women who were 40–69 years of age with a strong family history of breast cancer and no genetic mutations and were referred for high-risk assessment in a population-based breast cancer screening program [7]. They evaluated the impact of incorporating breast tissue density into risk assessment and found that 5.8% women had never had a screening mammogram. Of those who had mammography, the eligibility of 16.8% (22/131) was affected by their breast tissue density; 7% women with dense breasts became eligible while 10% with non-dense tissue became ineligible. The incorporation of density into risk stratification allowed for improved access to supplemental screening with breast MRI in women with dense breast tissue.

#### **5. Stage of Breast Cancer and Screening**

Wilkinson et al. evaluated the stage of breast cancer at diagnosis in a study of 55,490 women aged 40–59 years in Canada from 2010 to 2017 [8]. Using the Canadian Cancer Registry, the authors found marked differences in the stages of breast cancer in women aged 40–49 years compared with those aged 50–59 years; there were significantly lower proportions of stage I BC (35.7 vs. 45.3%; *p* < 0.001), and greater proportions of stage II (42.6 vs. 36.7%, *p* < 0.001) and stage III (17.3 vs. 13.1%, *p* < 0.001) in women in their 40s compared with the 50s. The authors evaluated the impact of organised screening programs on the stage of breast cancer at diagnosis. Jurisdictions that included women in their 40s in population-based screening programs had higher proportions of stage I (39.9% vs. 33.3%, *p* < 0.001) and lower proportions of stages II (40.7% vs. 43.7%, *p* < 0.001), III (15.6% vs. 18.3%, *p* < 0.001) and IV (3.9 vs. 4.6%, *p* = 0.001) in women 40–49 years old compared with their peers in the urisdictions that did not include them. A downstream impact was also seen in women in the 50s where screening practices for women aged 40–49 affected women aged 50–59 years; jurisdictions that did not screen women in their 40s had higher proportions of stage II (37.2% vs. 36.0%, *p* = 0.003) and stage III (13.6% vs. 12.3%, *p* < 0.001) in women aged 50–59 years as compared with programs that included the women in their 40s.

#### **6. Knowledge about Screening and the Overdetection of Breast Cancer**

Alenezi et al. performed a cross-sectional study in Saudi Arabia among 414 randomly selected female healthcare workers to assess their level of knowledge, attitude to breast cancer and barriers to mammography screening [9]. A high rate of a lack of knowledge was found, with 48.6% of the health care workers having a very low knowledge of breast cancer, and there was a significant negative correlation between a lack of knowledge and barriers to screening. The most important barriers related to screening included apprehension about radiation exposure (57%), fear of pain related to the mammographic examination (55.8%), fear of discovering breast cancer (57.2%) and fear of not knowing the procedure (48%). Logistic regression analysis found that physicians (*p* < 0.016) and workers older than 30 years of age (*p* < 0.03) were significantly more likely to have higher awareness about mammograms. This information may help target educational programs to improve mammography screening.

One of the most cited harms of breast cancer screening is that caused by the overdiagnosis or the overdetection of a breast cancer that would not have otherwise been found without screening, and that would not have led to the harm or death of the woman. Yaffe and Mainprize [10], in an excellent review, explore the phenomenon of overdetection, the methods for accurate estimation and the reasons for the variability in published estimates,

including the very high value used by the Canadian Breast Cancer Screening Studies (CNBSS) [11] that inform the Canadian Task Force on Preventive Health Guidelines for Breast Cancer Screening. They demonstrate unequivocally that in situ carcinomas are the most common cause of overdetection and should not be overtreated, and that overdetection is a far greater problem in older than younger women due to more competing causes of death in the older ages.
