Prevention of Breast Cancer (Part I): Epidemiology, Risk Factors, and Risk Assessment Tools

Tirona, Maria Tria; Sehgal, Rajesh; Ballester, Oscar F.

doi:10.3109/07357907.2010.494321

Cited by 64 publications

(47 citation statements)

References 69 publications

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“…The main cause of this mortality is the metastatic spread to other organs (1). Metastasis occurs when tumor cells acquire invasive features (2) and the ability to escape from antitumor immunity (3,4).…”

Section: Introductionmentioning

confidence: 99%

Human breast cancer cells enhance self tolerance by promoting evasion from NK cell antitumor immunity

Mamessier¹,

Sylvain²,

Thibult³

et al. 2011

J. Clin. Invest.

549

494

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NK cells are a major component of the antitumor immune response and are involved in controlling tumor progression and metastases in animal models. Here, we show that dysfunction of these cells accompanies human breast tumor progression. We characterized human peripheral blood NK (p-NK) cells and malignant mammary tumor-infiltrating NK (Ti-NK) cells from patients with noninvasive and invasive breast cancers. NK cells isolated from the peripheral blood of healthy donors and normal breast tissue were used as controls. With disease progression, we found that expression of activating NK cell receptors (such as NKp30, NKG2D, DNAM-1, and CD16) decreased while expression of inhibitory receptors (such as NKG2A) increased and that this correlated with decreased NK cell function, most notably cytotoxicity. Importantly, Ti-NK cells had more pronounced impairment of their cytotoxic potential than p-NK cells. We also identified several stroma-derived factors, including TGF-β1, involved in tumor-induced reduction of normal NK cell function. Our data therefore show that breast tumor progression involves NK cell dysfunction and that breast tumors model their environment to evade NK cell antitumor immunity. This highlights the importance of developing future therapies able to restore NK cell cytotoxicity to limit/prevent tumor escape from antitumor immunity. IntroductionBreast cancer (BC) is the primary cause of cancer deaths in women. The main cause of this mortality is the metastatic spread to other organs (1). Metastasis occurs when tumor cells acquire invasive features (2) and the ability to escape from antitumor immunity (3, 4). Defects in antitumor immunity may also facilitate BC occurrence. Indeed, mice deficient in IFN-γ production spontaneously develop mammary tumors (5). Breast tumor cells transplanted into NOD/SCID mice (which lack adaptive immunity) form noninvasive tumors, whereas the same cells transplanted into NOD/SCID/γ-c null mice (no adaptive immunity and no NK cells) form invasive tumors that metastasize rapidly (6). This effect is strictly dependent on NK cells (7). Similarly, in a highly metastatic model, BC metastasized to the lung only after elimination of NK cells by Tregs (8).Advanced BC patients show defects in antitumor immunity, such as alterations of DC maturation (9) and an increase in Treg infiltrates (10). Major impairment of peripheral blood NK cell maturation and cytotoxic functions has also been reported in metastatic BC (11). Several gene expression profiling studies have shown that a better outcome is associated with a strong cytotoxic infiltrate containing NK cells (12)(13)(14)(15). These data suggest that BC progression is linked to antitumor immunity efficiency and particularly to NK cells. However, the precise relationships between NK cells and BC progression in humans have not been studied so far.

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Section: Introductionmentioning

confidence: 99%

Human breast cancer cells enhance self tolerance by promoting evasion from NK cell antitumor immunity

Mamessier¹,

Sylvain²,

Thibult³

et al. 2011

J. Clin. Invest.

549

494

View full text Add to dashboard Cite

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“…Breast cancer remains the leading cause of death for women of 35 to 65 years old (1). Gene expression studies have shown the heterogeneity of the disease and identified at least 5 clinically relevant molecular subtypes of breast tumors: luminal A, luminal B, ERBB2, basal, and normal-like (2).…”

Section: Introductionmentioning

confidence: 99%

Human Breast Tumor Cells Induce Self-Tolerance Mechanisms to Avoid NKG2D-Mediated and DNAM-Mediated NK Cell Recognition

et al. 2011

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Breast cancer is the leading cause of death for women between the ages of 35 to 65. This is mostly due to intertumor heterogeneity and the lack of specific therapies for all subtypes. However, some breast cancers with an unexpected good prognosis are associated with enhanced antitumor immunity in situ. We studied whether breast cancer subtypes might have different susceptibilities to natural killer (NK) cells' antitumor immunity. We collected a large public set of microarray data for primary breast tumors and determined NK cell ligand expression. We found that despite heterogeneous levels of inhibitory HLA members, NKG2D ligands and DNAM ligands are expressed in virtually all breast tumor subtypes. Functional experiments in breast cancer subtypes expressing various levels of NK cell ligands showed that NK-mediated cytotoxicity is mainly HLA, NKG2D, and DNAM dependent. In parallel, we showed that cell lines and primary breast tumor cells secrete soluble inhibitory factors that alter NK cell functions. Finally, we showed that these mechanisms of escape occur in vivo in the MMTV-Neu model of spontaneous murine breast cancer. Our study shows that breast cancer cells, independent of the subtype, have developed different mechanisms to escape from NK cells' antitumor immunity. These results emphasize the role of NK cells in breast tumor clearance and underlie the importance of devising future therapy aiming at enhancing NK cell-mediated recognition in parallel with the prevention of the tumor-editing process.

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“…Latin America and the Caribbean are ranked in the middle, with an age-standardized incidence rate of 40 per 100,000 women [2]. As documented in the literature, a mixture of demographic, hereditary, economic, environmental, and lifestyle risk factors account for this variability [3]. However, differences in the capacity of a country's health system for detection and diagnosis, as well as case and death registration, also affect the disease burden.…”

Section: Introductionmentioning

confidence: 99%

A Review of Breast Cancer Care and Outcomes in Latin America

Justo¹,

et al. 2013

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This review presents an overview of breast cancer care, burden, and outcomes in Latin America, as well as the challenges and opportunities for improvement. Information was gleaned through a review of the literature, public databases, and conference presentations, in addition to a survey of clinical experts and patient organizations from the region. Breast cancer annual incidence (114,900 cases) and mortality (37,000 deaths) are the highest of all women's cancers in Latin America, and they are increasing. Twice as many breast cancer deaths are expected by 2030. In Peru, Mexico, Colombia, and Brazil, diagnosis and death at younger ages deprives society of numerous productive years, as does high disease occurrence in Argentina and Uruguay. Approximately 30%-40% of diagnoses are metastatic disease. High mortality-to-incidence ratios (MIRs) in Latin America indicate poor survival, partly because of the late stage at diagnosis and poorer access to treatment. Between 2002 and 2008, MIRs decreased in all countries, albeit unevenly. Costa Rica's change in MIR outpaced incidence growth, indicating impressive progress in breast cancer survival. The situation is similar, although to a lesser extent, in Colombia and Ecuador. The marginal drops of MIRs in Brazil and Mexico mainly reflect incidence growth rather than progress in outcomes. Panama's MIR is still high. Epidemiological data are scattered and of varying quality in Latin America. However, one could ascertain that the burden of breast cancer in the region is considerable and growing due to demographic changes, particularly the aging population, and socioeconomic development. Early diagnosis and population-wide access to evidence-based treatment remain unresolved problems, despite progress achieved by some countries. The Oncologist 2013;18: 248 -256 Implications for Practice: Breast cancer imposes a heavy epidemiological, clinical, and economic burden on Latin American societies, and the situation will only worsen in the foreseeable future. Physicians and decision makers alike need to prepare to provide better care to more women as incidence of the disease grows and health care coverage expands. The main challenges to be addressed are barriers to early diagnosis and access to evidence-based treatment alternatives in a multidisciplinary way. Because breast cancer in Latin America affects women at younger ages than in Europe or North America and frequent population-based mammographic screening is not a reality, raising awareness is everyone's job, from the general practitioners to the oncologists, from the non-governmental organizations to the policy makers, from every woman to every man. INTRODUCTIONThe burden of breast cancer, as well as the management and organization of breast cancer care in 18 countries, was presented recently in the Global Breast Cancer Report [1]. Breast cancer is the most common form of cancer in women; with 5.2 million survivors(5yearsfollowingdiagnosis),itremainsthemostprevalent cancer in the world. In 2008, a total of 1.38 million new...

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Prevention of Breast Cancer (Part I): Epidemiology, Risk Factors, and Risk Assessment Tools

Cited by 64 publications

References 69 publications

Human breast cancer cells enhance self tolerance by promoting evasion from NK cell antitumor immunity

Human breast cancer cells enhance self tolerance by promoting evasion from NK cell antitumor immunity

Human Breast Tumor Cells Induce Self-Tolerance Mechanisms to Avoid NKG2D-Mediated and DNAM-Mediated NK Cell Recognition

A Review of Breast Cancer Care and Outcomes in Latin America

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