Secondary Logo

Journal Logo

Review Article

Breast cancer in global health: beyond diversity and inequality

Liu, Lin MD; Kawashima, Masahiro MD, PhD; Toi, Masakazu MD, PhD

Author Information
International Journal of Surgery: Global Health: November 2020 - Volume 3 - Issue 6 - p e32
doi: 10.1097/GH9.0000000000000032
  • Open

Abstract

Breast cancer is the most frequently diagnosed cancer in 154 countries and the leading cause of cancer death in over 100 countries1. The standardization of surgery, adjuvant radiotherapy, and systemic therapy has been strongly established based on the understanding that breast cancer is a type of systemic disease. In parallel, advances in genomics have not only deepened the understanding of breast biology but also dramatically impacted the path toward risk reduction. In this review, we summarize global trends in epidemiology, screening, prevention, diagnosis, and therapeutics regarding breast cancer. It would help the readers deepen their understanding of breast cancer, especially its equality and diversity across the world.

Epidemiology

Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death among women. According to GLOBOCAN 2018, about 2,100,000 women were estimated to be newly diagnosed with breast cancer, accounting for 24% of all incidences of cancer among women. About 630,000 women were estimated to die due to breast cancer (15% of total cancer deaths)1.

There are substantial differences in breast cancer incidence and mortality depending on region. According to GLOBOCAN 2018 estimates, the incidence is higher in western countries, such as Australia/New Zealand (94.2/100,000), Northern Europe (90.1/100,000), Western Europe (92.6/100,000), Southern Europe (80.3/100,000), and North America (84.8/100,000). Contrastingly, it is lower in South America (56.8/100,000), Africa (27.9–48.9/100,000), and Asia (25.9–45.3/100,000). However, the incidence in the latter regions has been rising quickly over recent decades.

Breast cancer incidence also varies depending on a region’s degree of development. The incidence is significantly higher in countries that score high/very high on the Human Development Index (HDI) compared with countries with low/medium HDI scores (54.4 vs. 31.3 per 100,000). In contrast, the standardized mortality rate is much lower in countries with high/very high HDI scores (11.6 vs. 14.9 per 100,000). This difference is attributed mainly to the prevalence of well-established screening programs and abundant medical services in countries with high HDI scores1.

The onset age of breast cancer also differs across countries. In most western countries, 48% of breast cancer cases are diagnosed at ages 50–692, with the risk of breast cancer progressively increasing around age 503. For instance, in the United States, the median age of diagnosis is 62 years, and 82% of breast cancers are diagnosed in women at age 50 or older. About 90% of breast cancer deaths occur in the same age group4. However, in Asian countries such as China and Japan, the peak of age-standardized incidence occurs at an earlier age than in western countries; most cases are concentrated at ages 45–69 (Fig. 1)5–7.

Figure 1
Figure 1:
Differences in age-standardized incidence of female breast cancer by country (created based on the information in World Health Organization5).

The incidence and mortality of breast cancer also differ depending on race and ethnicity. In the United States, the incidence is the highest in Whites, followed by Blacks, Hispanics, and Asians/Pacific Islanders. Nevertheless, mortality is highest in Blacks, followed by Whites, Hispanics, and Asians/Pacific Islanders. The mortality rate of Whites and Blacks is more than double that of Asian/Pacific women (Fig. 2)4. A higher proportion of triple-negative breast cancers (TNBCs) in Blacks may partially explain this difference in mortality (Fig. 3)4. A similar trend can be found in African countries where the frequency of TNBCs is significantly high and many women are diagnosed at a young age. Unfortunately, the relevant genetic predisposition that may explain the higher incidence of TNBCs in women having African ancestry has not been identified8–10.

Figure 2
Figure 2:
Female breast cancer incidence and mortality rates by race in the United States (created based on the information in World Health Organization4). Incidence (2012–2016); mortality (2013–2017). AIAN indicates American Indian/Alaskan Native; API, Asian/Pacific Islander; NHB, non-Hispanic Black; NHW, non-Hispanic White.
Figure 3
Figure 3:
Difference in the proportion of breast cancer subtypes by race in the United States (created based on the information in World Health Organization4). AIAN indicates American Indian/Alaskan Native; API, Asian/Pacific Islander; NHB, non-Hispanic Black; NHW, non-Hispanic White.

Worldwide, the mean breast cancer mortality rate was estimated to be 13.77/100,000 in 1990, increasing by about 0.7/100,000 a year between 1990 and 2015. The total number of breast cancer deaths is still increasing in many countries, especially in middle- or low-income regions. Therefore, the worldwide increase in mortality may be partially due to the increase of breast cancer incidence in developing countries with insufficient medical resources11–14. In fact, the mortality rate is actually decreasing or stable in high-income countries (Fig. 4)11,15. From 2002 to 2012, breast cancer mortality declined from 17.9/100,000 to 15.2/100,000 in Europe. It is estimated to decrease further in 2020 (13.4/100,000). Mortality also declined in North America and Oceania, where it is predicted to reach 11–12/100,000 in 2020 (vs. 14/100,000 in 2012). No significant changes were observed in mortality in Japan and Korea, where mortality has been relatively low (under 10/100,000)12,13. According to statistics from 2008 to 2012 in China, during which the economy was quickly expanding, breast cancer incidence and mortality were 42.67/100,000 and 10.36/100,000, respectively. While the incidence had increased by 30.56%, the mortality had not increased significantly from 2003 to 201216. An estimate from the United States reported that between 384,000 and 614,500 breast cancer deaths had been averted through mammography screening and improved treatment between 1989 and 201817.

Figure 4
Figure 4:
Country-specific differences in age-standardized female breast cancer mortality between 1985 and 2020 (created based on the information in World Health Organization15).

These findings suggest that it is reasonable to establish individualized screening systems based on the age and race characteristics of each country, in addition to other possible factors. To reduce worldwide breast cancer death, it is important to address the unequal distribution of medical resources and funding as well as the gap in accessibility to the latest knowledge on breast cancer management.

Pathologic diagnosis and molecular subtyping

In the latest update of breast cancer classification by the World Health Organization, the importance of molecular subtyping is emphasized, primarily based on estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 (HER2) status18. Meanwhile, traditional prognostic indicators, such as tumor size (T), lymph node status (N), and the Nottingham grading system, are still deemed important19.

Molecular subtyping can sufficiently predict the biological behavior of tumors. Based on gene expression profiling, breast cancers have been classified into at least 4 subtypes: luminal-A and B, basal-like, normal breast-like, and ERBB2+ subtype20. Generally, due to the availability and cost effectiveness of gene expression profiling, immunohistochemistry is commonly used as an alternative. The St. Gallen International Expert Consensus Meeting from 2007 to 2011 highlighted the classification of breast cancer based on the immunohistochemistry of estrogen receptor, progesterone receptor, HER2, and Ki-67 labeling index and its usefulness in risk prediction and tailoring adjuvant treatment21. In 2011, a multigene assay known as oncotype DX was proposed as a useful tool to better predict the benefit of adjuvant chemotherapy for the luminal subtype21,22. Currently, oncotype DX and MammaPrint tests, with a higher level of evidence, are recommended by guidelines of the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology, and the European Society of Medical Oncology (ESMO)23–25.

To date, various studies have been performed to further classify breast cancer subtypes, especially for TNBCs in which the proper molecular target has not been identified. TNBCs are currently recognized as highly heterogenous. Based on the gene expression profiling of 21 breast cancer data sets and 587 TNBC cases, Lehmann et al26 identified 6 TNBC subtypes exhibiting different responses to therapy: basal-like 1/2 (BL1 and BL2), mesenchymal, immunomodulatory, mesenchymal stem-like, and luminal androgen receptor subtype. Jiang et al27 classified TNBCs into 4 subtypes: luminal androgen receptor, immunomodulatory, basal-like immune-suppressed, and mesenchymal-like, which could provide the opportunity for subtype-specific treatment. They also uncovered ethnic differences in the distribution of these subtypes by comparing the Chinese cohort to the Cancer Genome Atlas (TCGA) cohort. This may be partially attributed to a diversity of country-specific outcomes. Identification via proper subtyping and type-specific targeted treatment for this malignant subgroup are warranted. The advances in molecular phenotyping and pathology are intensively reviewed elsewhere, please refer to previously published reviews28–32.

Screening

As discussed, the decrease in breast cancer mortality observed in western countries has been achieved mainly through advances in screening and adjuvant therapy33,34. A breast screening program should include breast awareness, risk assessment, clinical examination, mammography, and magnetic resonance imaging (MRI) for selected patients35. Presently, multiple guidelines have recommend routine mammography instead of physical examination lacking in sufficient evidence36–38. All organizational guidelines have equally recommended mammography for women aged between 50 and 69 years (once every 1 to 2 y). However, for women aged between 40 and 49 years, some guidelines have begun to stop regularly recommending mammography due to a lack of sufficient evidence for this age group. The clinical benefit of mammography for women under 40 and over 75 years is similarly in question. In order to determine the proper age for active screening, clinicians must take into account the patient’s personal risk (dense breast, genetic background, familial history, etc.) and the age-specific pattern of breast cancer incidence in the country of residence36–38.

Besides conventional mammography, the feasibility of using ultrasonography (US), digital breast tomosynthesis (DBT), and MRI for screening a specific population has been questioned. An American observational cohort study reported that the cancer detection and interval cancer rates were not different between mammography screening alone and mammography plus US; and mammography plus US showed a higher false-positive biopsy rate and lower positive prediction values. The authors concluded that the benefits of supplemental ultrasonography screening do not seem to outweigh the associated harms for a relatively young population39. However, the Japan Strategic Anti-cancer Randomized Trial, a randomized controlled trial that compared mammography alone to mammography plus US, showed that the adjunctive US increased the sensitivity and detection rate of early cancers in Japanese women aged 40–49. Therefore, US should be considered as a screening method for Japanese and possibly Asian women, in general, in this age group. For other women, a risk estimate would be very important. Since US is largely dependent on the skills of technicians, its usefulness should be further examined with respect to each specific country or region40,41.

DBT, a new mammography technology equipped with 3-dimensional image reconstruction, has shown improved specificity and cancer detection rates across all age and breast density groups. Compared with conventional mammography, DBT can detect invasive cancer at an earlier stage, particularly for women aged 40–4942. However, due to the increased radiation dose it employs, DBT may be potentially harmful. Overall, DBT and contrast MRI have been recognized as an alternative for the confirmed high-risk group. NCCN guidelines recommend an annual MRI and DBT specifically for women with a known genetic predisposition to breast cancer or other confirmed risk factors. It is important to note that physicians should take into account the potential harm related to gadolinium-based contrast when considering MRI for breast screening.

Along with advances in imaging technology for breast screening, we must consider the variations in epidemiological characteristics, economics, and diagnostic performance (ie, number and skill level of breast radiologists and pathologists) within each country. Furthermore, we need to keep in mind that improvement in breast cancer detection does not necessarily translate into survival benefit. For instance, a recent study suggested that both the detection of low-grade ductal carcinoma in situ and its subsequent surgery were unlikely to yield survival benefit43. How best to minimize the potential harms stemming from overtreatment needs to be further investigated.

Prevention

Breast cancer prevention approaches include lifestyle modifications, chemoprophylaxis, and prophylactic mastectomies for specific populations. To date, obesity (especially in postmenopausal women), height in adulthood, radiation exposure, benign tumor disease (proliferative lesion with atypia), family history of breast cancer, hormone replacement therapy, and mammographic density are recognized as risk factors for breast cancer44. Growing evidence suggests that women may be able to reduce their risk by choosing a healthy lifestyle that involves avoiding alcohol, quitting smoking, exercising, changing food preferences (eg, increasing soy intake), and proper sleep45–48. Studies have also suggested that ambient air pollution and consumption of sugary drinks and red meat were positively associated with an increased risk49–51. However, it should be noted that these findings may be biased due to factors such as study population and exposure period—further confirmation is needed. In addition, parity, younger age at first birthing, and lactation can reduce the risk of breast cancer. However, some studies have suggested that first parity at an older age (over 30 y) could result in an increased breast cancer risk lasting at least 10 years after delivery52,53. It should be noted that the age of first parity tends to be delayed in many countries.

For the specific population with familial/genetic risk factors or those judged as high-risk by adequate cancer risk assessment models, pharmacological or surgical prevention could be considered. Based on the results of the National Surgical Adjuvant Breast and Bowel Project prevention trial, the Study of Tamoxifen and Raloxifene trial, the Mammary Prevention 3 trial, and the International Breast Cancer Intervention Studies-II trial, the NCCN guideline recommends the use of tamoxifen in premenopausal or postmenopausal women at least 35 years old with a ≥1.7% 5-year risk for breast cancer determined by the modified Gail model—or who have a history of lobular carcinoma in situ. Other studies report that anastrozole and exemestane could be considered for postmenopausal women54–57. In addition, proper monitoring of patients is essential to detect breast cancer or associated adverse events and to deliver timely adequate management.

Mutations in known breast cancer risk genes such as BRCA1/2, TP53, and PTEN are strong indicators for surgical prevention (Table 1)58–60. The distribution of these genetic predispositions may be slightly different across countries. The frequency of BRCA1 and BRCA2 mutations in unselected breast cancer patients has been reported as 3.2% and 3.1% in the United States, 1.0% and 1.9% in Italy, 1.45% and 2.71% in Japan, and 1.8% and 3.5% in China, respectively61–64. Several risk models have been developed to date: the modified Gail model, the Claus model, the BRCAPRO model, the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm, and the Tyrer-Cuzick model65–69. Different models have their adaptive populations. For example, the Gail model, which is most commonly used, is not applicable for with a significant family history45. Each risk model is developed from a retrospective epidemiological dataset collected from a particular country. Thus, a model’s performance could vary depending on the applied population. Each country or region should test which model would be most applicable to its residents, or consider developing a risk model based on its own epidemiological characteristics.

Table 1 - Known genetic predispositions associated with breast cancer and ovarian cancer.
Evidence level Breast cancer Ovarian cancer
Sufficient ATM, BRCA1*, BRCA2*, CDH1*, PALB2*, PTEN*, STK11*, TP53* BRCA1, BRCA2, BRIP1, MSH2, MLH1, MSH6, PMS2, EPCAM, RAD51C, RAD51D, STK11
Potential or controversial BARD1, CHEK2, NBN, NF1, RAD51D ATM
Unknown or unrelated BRIP1, MSH2, MLH1, MSH6, PMS2, EPCAM, RAD51C BARD1, NBN, PALB2
The table was created based on the information of Brisken and colleagues53–55.
*Indicates genes with an over 5-fold relative risk of breast cancer. Surgical risk reduction may be considered for this segment of the population under full discussion.

Currently, the NCCN, ESMO, Chinese, and Japanese breast cancer societies have recommended considering risk-reducing mastectomy (RRM) for women with the pathogenic variants, such as BRCA1/2 mutation44,45,70,71. Some guidelines have stated that RRM for women without a known genetic predisposition is worth considering if they are estimated to be high-risk (ie, women with a relevant family history, a past history of thoracic radiotherapy, etc.). Because of lack of high-quality evidence in this area, precise assessment of lifetime risk and careful discussion regarding potential benefits and harms with patients is important. When considering RRM, proper breast reconstruction should be offered upon the patients’ request whenever possible.

Current therapeutics

Major recent advances in breast cancer treatment can be summarized as follows: (1) implementation of minimally invasive surgery, (2) optimization of systemic treatment under the guidance of molecular diagnosis, and (3) establishment of a multidisciplinary team for decision-making. Here, we will briefly review the advances in current therapeutics and discuss the importance of multidisciplinary networking to improve breast cancer outcomes on a global scale. More comprehensive and detailed information on recent advances in therapeutics are discussed in elsewhere30–32,72–77.

The application of breast-conserving surgery (BCS) and sentinel lymph node biopsy are recent developments in breast surgery78. Nevertheless, several issues remain to be unanswered. Regarding BCS, a novel approach that facilitates precise tumor localization and margin assessment is warranted to reduce re-excision rates as well as local recurrence, especially after neoadjuvant treatment79,80. Introduction of sentinel lymph node biopsy has massively reduced the number of unnecessary axillary clearances. Moreover, the Austrian Breast and Colorectal Cancer Study Group Z0011 trial reported a further decrease of axillary clearances in node-positive patients who underwent BCS81. However, whether a similar strategy is applicable for patients with advanced cases, patients who underwent mastectomy without radiation, and patients who underwent BCS after neoadjuvant treatment is unknown79.

For HER2-positive breast cancers, the emergence of a HER2-targeted antibody, trastuzumab, dramatically changed the prognosis82. Currently, based on the results of the Adjuvant Paclitaxel and Trastuzumab and HER plus taxotere and cyclophosphamide trial, chemotherapy regimens tend to be weakened for low-risk populations83,84. However, for high-risk populations (commonly defined as node-positive), the addition of pertuzumab, another HER2-targeting antibody, to trastuzumab in adjuvant treatment significantly improved invasive-disease–free survival85. The addition of pertuzumab in neoadjuvant therapy has significantly improved the pathologic complete response (pCR) rate although its survival benefit remains to be further explored86–88. Patients who did not achieve pCR by neoadjuvant chemotherapy with trastuzumab can benefit from switching to trastuzumab emtansine, an antibody-drug conjugate targeting HER289.

Dose-dense chemotherapy regimens based on combinations of taxanes and anthracyclines are currently the standard treatment for TNBCs90. Neoadjuvant treatment is preferred for advanced patients in order to better predict their prognosis23. For patients who did not achieve pCR, the addition of capecitabine could improve survival. Poly ADP ribose polymerase inhibitors have improved disease progression of metastatic TNBC patients with germline BRCA1/2 mutations91,92. Use of an immune checkpoint inhibitor combined with chemotherapy is expected to improve the outcomes of TNBCs, but it is still under investigation. For advanced/metastatic TNBCs, the combination of a PD-L1 inhibitor, atezolizumab, and nab-paclitaxel improved survival for PD-L1-positive TNBCs93. The addition of a PD-1 inhibitor, pembrolizumab, significantly increased the pCR rate (64.8% vs. 51.2%) of neoadjuvant treatment for early TNBCs94.

A major recent advancement in adjuvant radiation therapy is hypo-fractionated whole breast irradiation (HF-WBI, typically 40–42.5 Gy in 15–16 fractions). The NCCN and American Society for Radiation Oncology guidelines have recommended HF-WBI; its use is now expanding to patients of any age, stage, and those who have undergone neoadjuvant chemotherapy23,95,96. The FAST-Forward study revealed that 26 Gy in 5 fractions was equivalent to 40 Gy in 15 fractions with respect to local tumor control and safety profile97. Recently, a gene expression–based prediction model for radiation sensitivity has been proposed to further optimize radiation dose98.

Finally, a multidisciplinary team (MDT) could be established to support patients as well as doctors in the process of decision-making. MDT has been proven to optimize the therapeutic schedule, shorten treatment time, improve patient satisfaction, and even improve their survival and quality of life99–102. To further expand the benefits of networking and cooperation, cross-regional MDT through international networking may also be beneficial. Because of the geographic, racial, ethnic, and cultural diversities within breast cancer, such a framework could bring equality and further individualization for breast management, as well as improvement of breast cancer prognosis on a global scale.

Ethical approval

This is a systematic review of breast cancer in global health and no ethical approval is required.

Sources of funding

L.L. is funded by the China Scholarship Council. M.K. and M.T. are funded by the Ministry of Health, Labor and Welfare KAKENHI Japan.

Author contribution

L.L. collected the relevant literature. L.L., M.K., and M.T. drafted the manuscript. All authors read and approved the final manuscript.

Conflict of interest disclosures

The authors declare that they have no financial conflict of interest with regard to the content of this report.

Research registration unique identifying number (UIN)

None.

Guarantor

Masahiro Kawashima.

References

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394–424.
2. Ferlay J, Soerjomataram I, Ervik M, et al. Cancer Incidence and Mortality Worldwide: IARC CancerBase. Lyon, France: International Agency for Research on Cancer. Version 11.2012. Available at: https://www.iarc.fr/. Accessed 2013.
3. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin 2015;65:87–108.
4. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019;69:7–34.
5. Ferlay J, Colombet M, Bray F. Cancer Incidence in Five Continents, CI5plus: IARC CancerBase No 9. Lyon, France: International Agency for Research on Cancer; 2018. Available at: http://ci5.iarc.fr.
6. Kruijshaar ME, Barendregt JJ. European Disability Weights Group. The breast cancer related burden of morbidity and mortality in six European countries: the European Disability Weights project. Eur J Public Health 2004;14:141–6.
7. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E359–86.
8. Der EM, Gyasi RK, Tettey Y, et al. Triple‐negative breast cancer in Ghanaian women: the Korle Bu teaching hospital experience. Breast J 2015;21:627–33.
9. Brinton LA, Figueroa JD, Awuah B, et al. Breast cancer in Sub-Saharan Africa: opportunities for prevention. Breast Cancer Res Treat 2014;144:467–78.
10. Newman LA, Kaljee LM. Health disparities and triple-negative breast cancer in African American Women: a review. JAMA Surg 2017;152:485–93.
11. Azamjah N, Soltan-Zadeh Y, Zayeri F. Global trend of breast cancer mortality rate: a 25-year study. Asian Pac J Cancer Prev 2019;20:2015–20.
12. Carioli G, Malvezzi M, Rodriguez T, et al. Trends and predictions to 2020 in breast cancer mortality in Europe. Breast 2017;36:89–95.
13. Carioli G, Malvezzi M, Rodriguez T, et al. Trends and predictions to 2020 in breast cancer mortality: Americas and Australasia. Breast 2018;37:163–9.
14. Lukong KE, Ogunbolude Y, Kamdem JP. Breast cancer in Africa: prevalence, treatment options, herbal medicines, and socioeconomic determinants. Breast Cancer Res Treat 2017;166:351–65.
15. WHO Mortality Database. World Health Organization. 2018. Available at: https://www.who.int/healthinfo/mortality_data/en/.
16. Zhang ML, Peng P, Wu CX, et al. Report of breast cancer incidence and mortality in China registry regions, 2008-2012. Zhonghua Zhong Liu Za Zhi 2019;41:315–20.
17. Hendrick RE, Baker JA, Helvie MA. Breast cancer deaths averted over 3 decades. Cancer 2019;125:1482–8.
18. Lakhani SR, Ellis I, Schnitt SJ, eds. WHO classification of tumours of the breast. World Health Organization Classification of Tumors, 4th ed. Lyon: IARC; 2012.
19. Hoon Tan P, Ellis I, Allison K, et al. The 2019 WHO classification of tumours of the breast. Histopathology 2020;77:181–5.
20. Sørlie T, Perou CM, Tibshirani R, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 2001;98:10869–74.
21. Goldhirsch A, Wood WC, Coates AS, et al. Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol 2011;22:1736–47.
22. Goldhirsch A, Winer EP, Coates AS, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol 2013;24:2206–23.
23. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer. NCCN.org. Version 2.2020. Available at: https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed February 5, 2020.
24. Andre F, Ismaila N, Henry NL, et al. Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: ASCO Clinical Practice Guideline Update—integration of results from TAILORx. J Clin Oncol 2019;37:1956–64.
25. Cardoso F, Kyriakides S, Ohno S, et al. Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2019;30:1194–20.
26. Lehmann BD, Bauer JA, Chen X, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest 2011;121:2750–67.
27. Jiang YZ, Ma D, Suo C, et al. Genomic and transcriptomic landscape of triple-negative breast cancers: subtypes and treatment strategies. Cancer Cell 2019;35:428–40.e425.
28. Rakha EA, Pareja FG. New advances in molecular breast cancer pathology. Semin Cancer Biol 2020:S1044-579X:30080–8.
29. Tsang JYS, Tse GM. Molecular classification of breast cancer. Adv Anat Pathol 2020;27:27–35.
30. Testa U, Castelli G, Pelosi E. Breast cancer: a molecularly heterogenous disease needing subtype-specific treatments. Med Sci (Basel) 2020;8:18.
31. Belizario JE, Loggulo AF. Insights into breast cancer phenotying through molecular omics approaches and therapy response. Cancer Drug Resist 2019;2:527–38.
32. Harbeck N, Penault-Llorca F, Cortes J. Breast cancer. Nat Rev Dis Primers 2019;5:66.
33. Plevritis SK, Munoz D, Kurian AW, et al. Association of screening and treatment with breast cancer mortality by molecular subtype in US women, 2000-2012. JAMA 2018;319:154–64.
34. Katalinic A, Eisemann N, Kraywinkel K, et al. Breast cancer incidence and mortality before and after implementation of the German mammography screening program. Int J Cancer 2020;147:709–18.
35. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: breast cancer screening and diagnosis. NCCN.org. Version 1.2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/breast-screening.pdf. Accessed May 17, 2019.
36. US Preventive Services Task Force. Screening for breast cancer: US Preventive Services Task Force recommendation statement. Ann Intern Med 2009;151:716–26.
37. Oeffinger KC, Fontham ET, Etzioni R, et al. Breast cancer screening for women at average risk: 2015 guideline update from the American Cancer Society. JAMA 2015;314:1599–614.
38. Lauby-Secretan B, Scoccianti C, Loomis D, et al. Breast-cancer screening-viewpoint of the IARC Working Group. N Engl J Med 2015;372:2353–8.
39. Lee JM, Arao RF, Sprague BL, et al. Performance of screening ultrasonography as an adjunct to screening mammography in women across the spectrum of breast cancer risk. JAMA Intern Med 2019;179:658–67.
40. Ohuchi N, Suzuki A, Sobue T, et al. Sensitivity and specificity of mammography and adjunctive ultrasonography to screen for breast cancer in the Japan Strategic Anti-cancer Randomized Trial (J-START): a randomised controlled trial. Lancet 2016;387:341–8.
41. Rebolj M, Assi V, Brentnall A, et al. Addition of ultrasound to mammography in the case of dense breast tissue: systematic review and meta-analysis. Br J Cancer 2018;118:1559–70.
42. Conant EF, Barlow WE, Herschorn SD, et al. Association of digital breast tomosynthesis vs digital mammography with cancer detection and recall rates by age and breast density. JAMA Oncol 2019;5:635–42.
43. Sagara Y, Mallory MA, Wong S, et al. Survival benefit of breast surgery for low-grade ductal carcinoma in situ: a population-based cohort study. JAMA Surg 2015;150:739–45.
44. Taira N, Arai M, Ikeda M, et al. The Japanese Breast Cancer Society clinical practice guidelines for epidemiology and prevention of breast cancer, 2015 edition. Breast Cancer 2016;23:343–56.
45. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: breast cancer risk reduction. NCCN.org. Version 1.2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/breast_risk.pdf. Accessed July 11, 2018.
46. Zheng X, Chen J, Xie T, et al. Relationship between Chinese medicine dietary patterns and the incidence of breast cancer in Chinese women in Hong Kong: a retrospective cross-sectional survey. Chin Med 2017;12:17.
47. Wei Y, Lv J, Guo Y, et al. Soy intake and breast cancer risk: a prospective study of 300,000 Chinese women and a dose–response meta-analysis. Eur J Epidemiol 2020;35:567–78.
48. Richmond RC, Anderson EL, Dashti HS, et al. Investigating causal relations between sleep traits and risk of breast cancer in women: mendelian randomisation study. BMJ 2019;365:l2327.
49. Chazelas E, Srour B, Desmetz E, et al. Sugary drink consumption and risk of cancer: results from NutriNet-Santé prospective cohort. BMJ 2019;366:l2408.
50. Lo JJ, Park YMM, Sinha R, et al. Association between meat consumption and risk of breast cancer: findings from the Sister Study. Int J Cancer 2020;146:2156–65.
51. Hwang J, Bae H, Choi S, et al. Impact of air pollution on breast cancer incidence and mortality: a nationwide analysis in South Korea. Sci Rep 2020;10:5392.
52. Albrektsen G, Heuch I, Hansen S, et al. Breast cancer risk by age at birth, time since birth and time intervals between births: exploring interaction effects. Br J Cancer 2005;92:167–75.
53. Brisken C. Progesterone signalling in breast cancer: a neglected hormone coming into the limelight. Nat Rev Cancer 2013;13:385–96.
54. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 1998;90:1371–88.
55. Vogel VG, Costantino JP, Wickerham DL, et al. Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: preventing breast cancer. Cancer Prev Res (Phila) 2010;3:696–706.
56. Goss PE, Ingle JN, Ales-Martinez JE, et al. Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med 2011;364:2381–91.
57. Cuzick J, Sestak I, Forbes JF, et al. Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial. Lancet 2014;383:1041–8.
58. Weiss A, Garber JE, King T. Breast cancer surgical risk reduction for patients with inherited mutations in moderate penetrance genes. JAMA Surg 2018;153:1145–6.
59. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: breast and ovarian. NCCN.org. Version 1.2019. Available at: https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf.
60. Couch FJ, Shimelis H, Hu C, et al. Associations between cancer predisposition testing panel genes and breast cancer. JAMA Oncol 2017;3:1190–6.
61. Palomba G, Budroni M, Olmeo N, et al. Triple-negative breast cancer frequency and type of BRCA mutation: Clues from Sardinia. Oncol Lett 2014;7:948–52.
62. Momozawa Y, Iwasaki Y, Parsons MT, et al. Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls. Nat Commun 2018;9:4083.
63. Kurian AW, Ward KC, Howlader N, et al. Genetic Testing and Results in a Population-Based Cohort of Breast Cancer Patients and Ovarian Cancer Patients. J Clin Oncol 2019;37:1305–15.
64. Sun J, Meng H, Yao L, et al. Germline Mutations in Cancer Susceptibility Genes in a Large Series of Unselected Breast Cancer Patients. Clin Cancer Res 2017;23:6113–9.
65. Gail MH, Costantino JP. Validating and improving models for projecting the absolute risk of breast cancer. Oxford University Press; 2001.
66. Claus EB, Risch N, Thompson WD. Autosomal dominant inheritance of early‐onset breast cancer. Implications for risk prediction. Cancer 1994;73:643–51.
67. Parmigiani G, Berry DA, Aguilar O. Determining carrier probabilities for breast cancer–susceptibility genes BRCA1 and BRCA2. Am J Hum Genet 1998;62:145–58.
68. Antoniou AC, Cunningham AP, Peto J, et al. The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions. Br J Cancer 2008;98:1457–66.
69. Tyrer J, Duffy SW, Cuzick J. A breast cancer prediction model incorporating familial and personal risk factors. Stat Med 2004;23:1111–30.
70. Paluch-Shimon S, Cardoso F, Sessa C, et al. Prevention and screening in BRCA mutation carriers and other breast/ovarian hereditary cancer syndromes: ESMO Clinical Practice Guidelines for cancer prevention and screening. Ann Oncol 2016;27(suppl 5):v103–110.
71. China Anti-Cancer Association. Breast cancer screening guideline for Chinese women. Cancer Biol Med 2019;16:822–4.
72. Ponde NF, Zardavas D, Piccart M. Progress in adjuvant systemic therapy for breast cancer. Nat Rev Clin Oncol 2019;16:27–44.
73. Greenwalt I, Zaza N, Das S, et al. Precision medicine and targeted therapies in breast cancer. Surg Oncol Clin N Am 2020;29:51–62.
74. Haussmann J, Corradini S, Nestle-Kraemling C, et al. Recent advances in radiotherapy of breast cancer. Radiat Oncol 2020;15:71.
75. Walsh EM, Smith KL, Stearns V. Management of hormone receptor-positive, HER2-negative early breast cancer. Semin Oncol 2020;47:187–200.
76. Cesca MG, Vian L, Cristovao-Ferreira S, et al. HER2-positive advanced breast cancer treatment in 2020. Cancer Treat Rev 2020;88:102033.
77. McCann KE, Hurvitz SA, McAndrew N. Advances in targeted therapies for triple-negative breast cancer. Drugs 2019;79:1217–30.
78. Cotlar AM, Dubose JJ, Rose DM. History of surgery for breast cancer: radical to the sublime. Curr Surg 2003;60:329–37.
79. Cutress RI, McIntosh SA, Potter S, et al. Opportunities and priorities for breast surgical research. Lancet Oncol 2018;19:e521–33.
80. Asselain B, Barlow W, Bartlett J, et al. Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials. Lancet Oncol 2018;19:27–39.
81. Giuliano AE, Ballman KV, McCall L, et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: the ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA 2017;318:918–26.
82. Moja L, Tagliabue L, Balduzzi S, et al. Trastuzumab containing regimens for early breast cancer. Cochrane Database Syst Rev 2012;4:CD006243.
83. Tolaney SM, Barry WT, Guo H, et al. Seven-year (yr) follow-up of adjuvant paclitaxel (T) and trastuzumab (H)(APT trial) for node-negative, HER2-positive breast cancer (BC). J Clin Oncol 2017;35(suppl 15):511.
84. Jones SE, Collea R, Paul D, et al. Adjuvant docetaxel and cyclophosphamide plus trastuzumab in patients with HER2-amplified early stage breast cancer: a single-group, open-label, phase 2 study. Lancet Oncol 2013;14:1121–8.
85. von Minckwitz G, Procter M, de Azambuja E, et al. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med 2017;377:122–31.
86. Gianni L, Pienkowski T, Im Y-H, et al. Five-year analysis of the phase II NeoSphere trial evaluating four cycles of neoadjuvant docetaxel (D) and/or trastuzumab (T) and/or pertuzumab (P). J Clin Oncol 2015;33(suppl 15):505.
87. Schneeweiss A, Chia S, Hickish T, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 2013;24:2278–84.
88. Shao Z, Pang D, Yang H, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive early or locally advanced breast cancer in the neoadjuvant setting: Efficacy and safety analysis of a randomized phase III study in Asian patients (PEONY). Cancer Res 2019;79(suppl 4):P6-17–17. SABCS18-P6-17-17. DOI: 10.1158/1538-7445.
89. von Minckwitz G, Huang CS, Mano MS, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med 2019;380:617–28.
90. Gray R, Bradley R, Braybrooke J, et al. Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37,298 women with early breast cancer in 26 randomised trials. Lancet 2019;393:1440–52.
91. Litton JK, Rugo HS, Ettl J, et al. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med 2018;379:753–63.
92. Robson M, Im SA, Senkus E, et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med 2017;377:523–33.
93. Schmid P, Rugo HS, Adams S, et al. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2020;21:44–59.
94. Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for early triple-negative breast cancer. N Engl J Med 2020;382:810–21.
95. Smith BD, Bellon JR, Blitzblau R, et al. Radiation therapy for the whole breast: executive summary of an American Society for Radiation Oncology (ASTRO) evidence-based guideline. Pract Radiat Oncol 2018;8:145–52.
96. Shaitelman SF, Lei X, Thompson A, et al. Three-year outcomes with hypofractionated versus conventionally fractionated whole-breast irradiation: results of a randomized, noninferiority clinical trial. J Clin Oncol 2018;36:3495–503.
97. Brunt AM, Haviland JS, Wheatley DA, et al. Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial. Lancet 2020;395:1613–26.
98. Scott JG, Berglund A, Schell MJ, et al. A genome-based model for adjusting radiotherapy dose (GARD): a retrospective, cohort-based study. Lancet Oncol 2017;18:202–11.
99. Chang JH, Vines E, Bertsch H, et al. The impact of a multidisciplinary breast cancer center on recommendations for patient management: the University of Pennsylvania experience. Cancer 2001;91:1231–7.
100. Chirgwin J, Craike M, Gray C, et al. Does multidisciplinary care enhance the management of advanced breast cancer?: evaluation of advanced breast cancer multidisciplinary team meetings. J Oncol Pract 2010;6:294–300.
101. Gabel M, Hilton NE, Nathanson SD. Multidisciplinary breast cancer clinics: do they work? Cancer 1997;79:2380–4.
102. Eaker S, Dickman PW, Hellstrom V, et al. Regional differences in breast cancer survival despite common guidelines. Cancer Epidemiol Biomarkers Prev 2005;14:2914–8.
Keywords:

Breast cancer; Global epidemiology; Incidence; Mortality; Screening, Prevention; Diagnosis; Genetic predisposition; Current therapeutics

Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of IJS Publishing Group Ltd.