Management of early breast cancer in the elderly

Breast cancer is the most common malignancy in women with an age related increase in incidence ranging from 1 in 50 at age 50 to 1 in 10 at age 80. This is particularly significant in view of the changing demographics in the western population, characterised by an aging population and increased life expectancy. However in spite of favourable prognostic factors and less aggressive biological behaviour, elderly breast cancer patients receive less aggressive treatment when compared with their younger counterparts. Appropriate treatment should be offered depending on physiological reserve and comorbidities. Primary endocrine treatment has been shown to be associated with significant morbidity in terms of disease progression. Prompt surgery and adjuvant treatment can decrease relapse and improve survival. Radiation therapy is shown to decrease local relapse and chemotherapy may have a role in a select group of patients with adverse prognostic factors. With incidence of breast cancer bound to increase in the elderly population, it is essential to establish optimum therapy in this cohort of patients as studies reveal good outcome from standard treatment.     

乳腺癌血清肿瘤标志物和循环肿瘤细胞检测的研究进展

 随着分子生物学的发展,乳腺癌的治疗正逐步进入分子分型治疗的时代,为了给患者提供更加有效的个体化治疗,研究者们不断努力寻找乳腺癌新的治疗靶点、疾病监控指标以及疗效预测和预后评估的指标,日益深入的研究显示血清肿瘤标志物和循环肿瘤细胞的检测在乳腺癌治疗中有重要价值。现就近年乳腺癌血清肿瘤标志物和循环肿瘤细胞检测的相关临床研究作一综述。     

Role of bisphosphonates in postmenopausal women with breast cancer

Data suggest that bisphosphonates protect bone health and may have anticancer activity in postmenopausal women during adjuvant breast cancer therapy. However, key questions remain surrounding the role of adjuvant bisphosphonates in breast cancer, including patient populations deriving benefit, timing/scheduling of therapy, and specific clinical benefits. PubMed, Embase, and San Antonio Breast Cancer Symposium databases provide study results that address these issues in postmenopausal women. Review of these data would aid physicians in providing optimal management of breast cancer in postmenopausal women. For example, recent data reinforce use of intravenous bisphosphonates concurrently with adjuvant endocrine therapy to ameliorate bone loss in recently postmenopausal or osteopenic postmenopausal women with early breast cancer. In contrast, clinical data for oral bisphosphonates have not provided support for using anti-osteoporosis doses in this setting, and the optimal dose is unclear. Additionally, current clinical data show improvements in disease outcomes with bisphosphonates in many studies, although not in all patient subsets. Strong support for the potential adjuvant anticancer benefits from bisphosphonates has been demonstrated in women with established menopause (i.e., very low circulating estrogen levels). Initiating bisphosphonates early and concomitantly with adjuvant therapy generally provided the greatest benefits. However, questions remain such as schedule of treatment and relative potency among the intravenous bisphosphonates and elucidation of the role of oral bisphosphonates, as well as ongoing studies that might provide clarification. This review addresses these controversies in the context of translational research, which may provide the rationale for ongoing studies and evolving treatment paradigms in this area.     

Comparison of recurrence and survival rates after breast-conserving therapy and mastectomy in young women with breast cancer

Multiple randomized trials have demonstrated that breast-conserving therapy with partial mastectomy and radiotherapy provides survival equivalent to that seen with mastectomy for patients with early-stage breast cancer. Breast-conserving therapy has been associated with better quality of life relative to mastectomy and has become the standard of care for patients with early-stage breast cancer. Young age has been identified as a risk factor for recurrence and death from breast cancer. Some studies have suggested that young women (less than 35 or 40 years of age) have inferior outcomes with breast-conserving therapy, implying that such women may be better served by mastectomy. On review of the available literature, there is no definitive evidence that mastectomy provides a consistent, unequivocal recurrence-free or overall survival benefit over breast-conserving therapy. However, available meta-analyses have not compared outcomes in young women specifically, and such analyses should be performed. In the interim, breast-conserving therapy is not contraindicated in young women (less than 40 years of age) and can be used cautiously; however, such women should be advised of the lack of unequivocal data proving that survival is equivalent to that with mastectomy in their age group.     

Factors used to select adjuvant therapy of breast cancer in the United States: an overview of age, race, and socioeconomic status.

Age, race, and socioeconomic status all play a role in decisions regarding breast cancer adjuvant therapy. Increasing age remains the major risk factor for breast cancer, while in very young women breast cancer may have a poorer prognosis, even when adjusted for disease stage and other variables. More than half of all new breast cancers in the United States occur in women older than 65 years. Because of the higher frequency of coexisting (comorbid) serious illness in older women, the benefits of adjuvant therapy get smaller as age increases. Adjuvant therapy with tamoxifen and/or chemotherapy can statistically significantly improve survival in older women, but older women are less likely to receive chemotherapy and are less likely to be offered participation in clinical trials. Efforts are now under way to overcome age bias among health care providers and to develop clinical trials focusing on older patients. Breast cancer mortality is higher in African-Americans than in white Americans. Although the biologic characteristics of breast cancer are worse in African-Americans, major differences in survival are related to socioeconomic factors and access to care. When matched for disease stage and other major clinical and biologic variables, African-American and white patients have similar survival rates. Few data are available on the effects of adjuvant treatment on early breast cancer outcomes in Hispanic Americans and Asian-Americans. Poverty and lack of insurance are surrogates for poor outcomes; major efforts are needed to guarantee all Americans high-quality cancer care.     

老年人乳腺癌

老年人乳腺癌与年轻人乳腺癌相比,恶性程度相对较低。临床以局部性或局部晚期癌较多。因老年患者生理变化,且常同时伴有其他疾病,治疗原则应选择对患者创伤及不良反应最小而能获得最大疗效的综合治疗,除基于疾病的分期外,要注重了解乳腺癌的生物学特征、患者体力情况、重要脏器器官功能及对拟定疗法的耐受能力。手术是可手术乳腺癌主要治疗手段之一,早期乳腺癌ER( )者,采用肿瘤局部扩大切除或加前哨淋巴结活检术(SLNB),术后加或不加放疗,辅助以内分泌治疗可达到满意控制肿瘤效果。局部晚期乳腺癌或肿瘤较大,ER( )者,可采用第三代芳香化酶抑制剂(3rdAI)行新辅助内分泌治疗,肿瘤缩小后采用缩小手术切除范围术式。对全身复发、转移高危及ER(-)患者,如体力情况尚好,可化疗。     

Racial disparities in female breast cancer in South Carolina: clinical evidence for a biological basis

Objective. Racial disparities in breast cancer outcomes are well documented: African-American (AA) women have markedly poorer survival than do European-American (EA) women. A growing literature suggests that AA women have, on average, tumors of more aggressive histopathology, even if discovered early. We investigated this in our South Carolina population. Methods. Tumor registry data for 1687 AA and EA women with breast cancers newly diagnosed during 2000–2002 at the two Palmetto Health hospitals in Columbia, SC, were reviewed. Results. Corresponding to our regional population, 31% of cancers were in AA women. In both racial groups, 19% were in situ. Among women with invasive cancers, AA women had significantly earlier age at diagnosis than did EA women. Fewer AA women had lobular carcinoma (p =0.001) or Her-2 over-expressing disease (7 versus 19%, p =0.001). Significantly more AA women had high-grade cancer, larger tumors, axillary metastases and ER negative/PR negative tumors. After controlling for T-stage, AA women were significantly more likely to have high-grade and/or ER negative disease. Detection of invasive cancers by screening mammogram was less frequent in AA women (40 versus 53%, p< 0.000), and in small ER negative cancers. Conclusions. At diagnosis, breast cancers in AA women tend to have the hallmarks of more aggressive and less treatable disease, even in small tumors, a pattern resembling that of breast cancers in younger EA women. Whatever the causes, these observations suggest breast cancer is biologically different in AA women. This may contribute substantially to the poorer outcomes in African-American women.     

Breast cancer in African American women: Epidemiology and tumor biology

Summary This review of published data on the epidemiology, pathology, and molecular biology of breast cancer in African American women seeks to identify how the etiology and presentation of the disease differ from those in white women. The crossover from higher to lower age-specific incidence rates in African American women at age 45 cannot be explained by current data on the distribution of risk factors. Data from six case-control studies suggest that the relative risks associated with both established and probable breast cancer risk factors are similar in African American and white women. Lower survival in African American compared to white women is primarily attributable to diagnosis at a later stage. However, evidence from a number of studies suggests that tumors in African American women may exhibit a more aggressive phenotype, which could also contribute to the survival disparity. Tumors in African American women are more likely to occur at a younger age, to be poorly differentiated and estrogen receptor negative, and to exhibit high grade nuclear atypia, more aggressive histology (more medullary and less lobular), and higher S-phase. Overexpression of p53 and erbB-2 occurs with similar frequency in African American and white women, although limited data suggest the former may exhibit different p53 mutation spectra. One study found high risk associated with a specific CYP1A1 polymorphism in African American but not white women. Additional studies of molecular differences in African American and white women are needed, with multifactorial assessment of the independent effects of molecular and conventional risk attributes.     

Breast cancer in elderly women (> or = 70 years): which treatment?

Breast cancer is a disease that affects women >70 years of age much more frequently than other age groups. Epidemiologic data show that more than 40% of breast cancers occur in the elderly. The optimal primary treatment for elderly patients with breast cancer is controversial and ranges from tamoxifen as sole therapy to surgery. Despite the high prevalence of the disease, the elderly have been excluded from clinical trials mainly for the presence of concurrent medical conditions that adversely affect treatment strategies. Since life expectancy continues to increase in western countries, an appropriate treatment that respects quality of life needs to be determined for the elderly age group. In the light of randomised and retrospective studies carried out to date, limited surgery without axillary dissection plus adjuvant tamoxifen seems to achieve, mainly for elderly patients with early stage breast cancer, a local-regional control rate comparable to that obtained with more aggressive therapeutic strategies. The results of ongoing prospective clinical trials will show whether or not conservative surgery without axillary clearance and tamoxifen may be routinely used for elderly patients with early breast cancer.     

Unique Features of Young Age Breast Cancer and Its Management

Young age breast cancer (YABC) has unique clinical and biological features that are not seen in older patients. Breast tumor biology is more aggressive and is associated with an unfavorable prognosis in younger women. The diagnosis of breast cancer is often delayed, resulting in their initial presentation with more advanced disease. Together, these characteristics lead to a poorer prognosis in younger women than in older women. Young women who receive breast-conserving therapy have a higher rate of local recurrence. Therefore, it is important to secure sufficient resection margins and consider boost radiotherapy to prevent local treatment failure. Based on age alone, patients with YABC should be regarded as high-risk cases, and they should be treated with adjuvant chemotherapy. Special considerations regarding psychosocial factors and fertility should be taken into account for young patients. This review discusses the major considerations and principles concerning the management of patients with YABC.     

Breast cancer in adolescents and young women

Breast cancer is very rare in adolescents and very young women. Less than 1% of all breast cancer cases occur before the age of 30 years (Natl Cancer Inst Monogr 16 (1994) 69). Invasive breast cancer occurring in women before the age of 35 years has a more aggressive biological behaviour and is associated with a worse prognosis than in older premenopausal women. Breast cancers in these young women are more frequently poorly differentiated, oestrogen-receptor (ER)-negative, have lymphovascular invasion and high proliferating fractions. Breast-conserving surgery in women <35 years old is associated with a higher risk of local recurrence than in older women. All young women should be considered at moderate-high risk by virtue of their age alone and offered adjuvant therapy. The long-term toxicity of adjuvant therapies is a particular concern when treating these women. The implications of possible fertility impairment and premature menopause require consideration when discussing adjuvant chemotherapy and endocrine therapy. Adolescents and young women are particularly vulnerable to emotional distress and psychosocial problems and should be provided with appropriate support. Young women who are at a potential high-risk of developing breast cancer such as those with germline mutations of BRCA1, BRCA2, TP53, PTEN or who have previously received mantle irradiation for Hodgkin's disease need close follow-up and are candidates for screening from a young age.     

Factors that influence the incidence of breast cancer in Arica, Chile (Review)

Breast cancer is a common disease estimated to occur in 1 in 9 women over their lifetime. Epidemiological research has identified a number of risk factors for breast cancer. Racial and ethnic differences in breast cancer mortality rates have been difficult to ascertain. The present review reports that there was an increase in the incidence of breast cancer in Arica, Chile, from 1997 to 2007, particularly in 2005, reaching 55.1% per 100,000 women, while the percentage decreased in 2006 and 2007. A greater percentage of breast cancer was found in individuals between 46 and 65 years of age when the population was distributed by age. The Indian population, Aymara, had only a 13.9% incidence of the disease. The incidence for breast cancer for patients with no family background reached approximately 88%, with or without Indian ethnicity, and 98.4% of these women did not have prior hormonal therapy. When the stage of the disease and the number of pregnancies were considered, results showed that there was an increase in the progression of the disease from stage I to stage III in women that had 1-3 pregnancies. Results also showed that 20.9 and 33.2% who received prior tamoxifen treatment were in stages I and IIA, respectively. The breast cancer incidence reached 42.4% when patients had a sister with the disease. It can be concluded that important differences in the risk factors of breast cancer should be identified in the future for a comparison with other biological factors, such as genetic and molecular factors. This may provide greater insight into breast cancer aetiology in different populations.     

Survival of young and older breast cancer patients in Geneva from 1990 to 2001

The effect of age on breast cancer survival is still a matter of controversy. Breast cancer in young women is thought to be more aggressive and to have worse prognosis but results from clinical research have been neither consistent nor definitive. In this study, we have assessed the impact of young age at diagnosis on tumor characteristics, treatment and survival of breast cancer. The study included 82 very young (< or = 35 years), 790 young (36-49), and 2125 older (50-69) women recorded between 1990 and 2001 at the Geneva Cancer Registry. Very young and young patients had more often stage II cancers (P = 0.009), poorly differentiated (P < 0.001) and estrogen receptor negative (P < 0.001) tumors. They were also more likely to receive chemotherapy (P < 0.001) and less likely to receive hormonal therapy (P < 0.001). Specific five-year survival was not different in the three groups (91%, 90%, and 89% for very young, young and older, respectively). When adjusting for all prognostic variables, age was not significantly related to mortality from breast cancer with a hazard ratio of 0.8 (95% CI: 0.3-2.0) for very young and 1.1 (95% CI: 0.8-1.4) for young patients compared to older women. Tumor stage, differentiation, estrogen receptor status, surgery, and radiotherapy were all independent determinants of breast cancer prognosis. We conclude that age is not an independent prognostic factor when accounting for breast tumor characteristics and treatment.     

Adjuvant therapy for very young women with breast cancer: response according to biologic and endocrine features

Incidence of breast cancer in patients aged < 20 years has been estimated to be 0.1 per 100,000 women. Reported incidences are 1.4 for women aged 20-24 years, 8.1 for women aged 25-29 years, and 24.8 for women aged 30-34 years. Younger patients have been found to have a more aggressive presentation of disease at diagnosis, which is associated with dire prognoses compared with those in premenopausal older patients. Several biologic features might explain the more aggressive behavior of breast cancer in younger patients: higher grade and higher expression of Ki67, higher occurrence of vessel invasion, and less expression of estrogen and progesterone receptors. Choice of adjuvant therapies for women aged <35 years with breast cancer is based on data derived from trials on cohorts of older patients. On average, the effect of chemotherapy for premenopausal patients is substantial: recent evidence suggested that very young women with endocrine-responsive tumors had a higher risk of relapse than older premenopausal patients with similar tumors. This was not the case for patients with endocrine-nonresponsive tumors, for which effects of chemotherapy were similar across ages. Very young women with this disease are faced with personal, family, professional, and quality-of-life issues that further complicate the phase of treatment decision-making. The development of more effective therapies for very young women with breast cancer requires tailored treatment investigations and research focused on issues specific to these patients.     

Variations in breast cancer treatment by patient and provider characteristics

Summary Guidelines for the optimal treatment of breast cancer have been publicized over the past 15 years, yet clinical practices continue to vary substantially in the United States. This article reviews the literature on variations in local and systemic treatment of breast cancer by patient and provider characteristics.Studies of local therapy have consistently demonstrated that older women are less likely than younger women to receive radiation therapy after breast-conserving surgery. Some studies have noted that black women are less likely than white women to receive breast-conserving surgery and less likely to receive radiation therapy after breast-conserving surgery. Rates of breast-conserving surgery vary three-fold among geographic regions and between teaching and non-teaching hospitals. Patients at smaller hospitals appear less likely to receive indicated radiation therapy.Patterns of systemic therapy have not been well described. Women over age 75 may not be receiving adequate hormonal therapy, but recent data are not available. Limited data suggest that rates of systemic therapy do not vary substantially by race or Hispanic ethnicity, but women without health insurance may not be receiving appropriate chemotherapy. Studies relating hospital and physician characteristics to the use of systemic therapy are sparse and inconclusive.In order to increase the proportion of women who receive optimal treatment for breast cancer and ensure greater equity, a more sophisticated understanding of variations in clinical practice will be required. These variations may arise from insufficient knowledge of or disagreement with guidelines among physicians, inadequate communication between physicians and patients, and individual preferences or clinical attributes of patients. Future studies will need to explore the dialogue between women and their physicians that leads to decisions about treatment of breast cancer.     

Epidemiology of breast cancer in young women

Breast cancer is mainly a postmenopausal disease, but in younger women breast tumors often exhibit more aggressive features and worse prognosis. Furthermore, high-risk and low-risk tumors present different age distributions suggesting that breast cancer comprises a mixture of two different disease processes. In agreement with this hypothesis, breast cancer presents different epidemiologic traits in pre- and postmenopausal women. Regarding racial distribution, incidence is higher in black women at younger ages in US, while the reverse is true among women older than 50 years. Genetic predisposition is a stronger risk factor in young women. On the contrary, nulliparity and obesity decrease the risk of early-onset breast cancers while are associated with higher incidence in older women. Epidemiologic data related with the hormonal exposure in utero suggest that the effect is stronger in early breast cancers. In most developed countries, breast cancer has shown an upward trend until recent years in postmenopausal women, while incidence rates in younger women have been stable. However, Spain is an exception to this rule: Spanish women younger than 45 years of age have registered a steady increase of breast cancer that may be related with the remarkable lifestyle changes experienced by women born in the second half of the twentieth century.     

Is Age Still the Deciding Factor? Commentary on “The Effect of Age on Delay in Diagnosis and Stage of Breast Cancer” by Partridge et al.

The study by Partridge et al., published in this edition of The Oncologist, is examined.Young breast cancer patients face multiple different challenges when diagnosed and when undergoing treatment for breast cancer than do postmenopausal patients. Very young breast cancer patients, especially those aged <35 years, have been described in multiple reports to have a worse prognosis [1–3]. Additionally, because women are not routinely recommended to consider initiating screening mammography until their 40s or 50s, a younger woman is more likely to develop a cancer at an advanced stage and to be diagnosed because of the onset of symptoms. There remains concern that a delay in diagnosis of breast cancer in a younger woman is one of the contributing factors to these worse outcomes in young breast cancer patients.It was estimated by the American Cancer Society that ∼5% of cases of breast cancer will be diagnosed each year in women aged <40 years [4]. Several case series have demonstrated worse outcomes in younger breast cancer patients. Nixon et al. [1] reported on 107 patients aged <35 years with either stage I or stage II breast cancer and compared them with their older counterparts. The younger patients were found to have a statistically significant greater recurrence risk and risk for developing distant metastatic disease. Kroman et al. [3] reported that younger women who had node-negative cancers or tumors <2 cm were significantly more likely to die from their cancer if they did not receive systemic adjuvant therapy. However, this effect was mitigated if they received cytotoxic therapy. Race may also play a factor in the diagnosis of breast cancer in young women. Black women have a twofold higher chance of being diagnosed at <35 years of age than white females. In addition, black women have higher presenting stages and higher mortality rates from breast cancer in the U.S. than white women [5, 6].When looking at the underlying biology of younger women with breast cancer, the majority of reports show a higher rate of hormone receptor–negative tumors [1–3] than in postmenopausal breast cancer patients. When evaluating very low-risk disease, such as node-negative tumors that are ≤1 cm, age was identified as an independent risk factor for the recurrence-free survival interval. This was more significant in women with human epidermal growth factor receptor (HER)-2⁺ and hormone receptor–positive tumors and was not demonstrated to be significant in patients with triple-negative tumors [7]. Additionally, Anders et al. [8] used microarray data from 784 women with early-stage breast cancers, again demonstrating lower percentages of hormone receptor positivity and higher grade tumors. There were 367 gene sets found to significantly differentiate the tumors arising in younger women from those in older women. Examples of gene sets that were differentiated by age included those encoding epidermal growth factor receptor and mammalian target of rapamycin as well as BRCA1, among many others [8]. This information was particularly intriguing and hypothesis generating regarding combination therapy that could take advantage of such pathways in younger breast cancer patients. Therefore, the question remains, is it truly the age of the patient herself that is the underlying cause of this described worse prognosis or is age just a surrogate marker for more aggressive tumor subtypes that occur more frequently in younger patients?Another confounding factor in this debate is the question surrounding a delay in diagnosis. There have been conflicting reports on whether or not a delay in diagnosis and a delay from the time of first symptom to the time of treatment initiation influence breast cancer prognosis. One large systematic review demonstrated that delays of 3–6 months from the time of diagnosis to the time of initiation of treatment were associated with a statistically significant lower 5-year survival rate [9]. However, it was noted that, in the included studies that did account for stage, a delay was not associated with a worse overall survival outcome. Younger patients who had not previously been designated to be high risk and had not undergone earlier screening would be expected to present with more advanced stages of disease than postmenopausal women whose cancer was diagnosed on screening mammography. In the most recent screening mammography recommendations by the U.S. Prevention Services Task Force, mammogram recommendations were changed to start after age 49, to increase the interval between screenings, and to individualize the decision for women in their 40s [10]. This change was a result of the lack of available randomized data showing a lower mortality rate with screening in this age group, although recently Hellquist et al. [11] used data collected from the Swedish mammography screening program to evaluate their experience with screening women aged 40–49 years and showed a relative risk for mortality for those who underwent screening of 0.71, which was statistically significant, and estimated that 1,252 women needed to be screened to save one life. There currently are no recommendations for screening mammography in women aged <40 years unless they have been identified to be at high risk for developing breast cancer, such as women with a hereditary predisposition to develop breast cancer, such as patients with BRCA1 or BRCA2 mutations. Therefore, as routine strategies for screening are currently evaluating women aged >40 years, except in special populations, younger women who develop breast cancer are more likely to present with clinical symptoms.In the current retrospective study by Partridge et al. [12], the authors use the National Comprehensive Cancer Center Network database to evaluate 21,818 women with breast cancer, stages I–IV, of whom 2,445 were aged ≤40 years. The purpose of the study was to evaluate if age alone was considered an independent risk factor for a delay from the time of the first symptom to the time that the woman sought treatment and was initially diagnosed with breast cancer. This study therefore asks a slightly different question: does age factor into actually seeking evaluation and undergoing diagnostic procedures? Additionally, the authors evaluated other socioeconomic factors such as race, education, employment status, and type of initial sign or symptom. When evaluating age as a factor in delay to breast cancer diagnosis, age ≤40 years old was initially found to be associated with a >60-day delay in diagnosis—odds ratio (OR), 1.52; 95% confidence interval (CI), 1.39–1.67; p < .0001. However, when the multivariate model was adjusted for the initial sign or symptom, there was no longer a statistically significant difference. Also in multivariate modeling, those women who had an initial sign or symptom had a significantly greater association with a >60-day delay in diagnosis (OR, 3.31; 95% CI, 3.08–3.56). Women with screening-detected tumors were more likely to be diagnosed with an earlier stage of breast cancer (64% of women diagnosed using screening were diagnosed with stage I tumors, compared with 28% of women who presented with an initial sign or symptom).This was a very well-conducted study using a very detailed database that spans several cancer centers throughout the U.S. The study has the expected limitations of a retrospective database study, including recall bias and the lack of information regarding previous screenings and whether or not patients had been identified as having a high risk for developing breast cancer. Also, women who were included had been referred to or sought treatment at a large comprehensive cancer center and may not reflect presentation patterns elsewhere. It would be interesting to note if there is any difference in time to delay not by age but by tumor biology. If a tumor has a more aggressive growth pattern, such as triple receptor–negative or HER-2⁺ tumor, will that influence more substantially the time to diagnosis? For this analysis, the authors did not include tumor receptor information in their modeling. Given the understanding of these inherent limitations, the study does provide insight as to whether or not age is a barrier to seeking treatment and being diagnosed with breast cancer.The failure of age to be consistently associated with a delay in diagnosis of breast cancer in this study when controlling for stage of disease leads back to the original concern: is it age or is it biology? If a delay does not appear to be the significant factor for young breast cancer patients and thus not likely to be the underlying cause of worse outcomes, the underlying biology of the disease that commonly presents in younger women should continue to be the main target. It will also be important to identify those women diagnosed at a young age with less biologically aggressive tumors who should be spared systemic therapy. In order to improve our therapies as well as to improve patient outcomes, we need to continue to develop strategies for identifying women at higher risk for developing breast cancer, for improving knowledge on the importance of family history, for improving genetic risk assessment, for identifying known and yet to be identified hereditary cancer syndromes, and, finally, for personalizing screening, prevention, and treatment strategies.See the accompanying article on pages 775–782 of this issue.     

Early breast cancer

Breast cancer remains a common disease throughout the world. Here we review new knowledge about early breast cancer obtained during the past 5 years. The prognosis of early breast cancer is generally favorable. Especially, ductal carcinoma in situ has been regarded as a non-life-threatening disease. Therefore, early diagnosis and early onset of the treatment has been important. Early age at menarche, late age at first birth, and late age at menopause are related to breast cancer risk. Examination by mammography and ultrasonography is still the most effective means of detection for premenopausal and postmenopausal women, respectively. Additionally, there have been important advances in MRI, sentinel lymph node biopsy, breast-conserving surgery, partial breast irradiation, neoadjuvant systemic therapy, and adjuvant systemic therapy. Another approach to keeping the disease under control is the elucidation of breast cancer's molecular biological features. Assessment of potential molecular targets can lead to early diagnosis and molecular targeted treatment.     

HER-2阳性炎性乳腺癌的靶向治疗进展

原癌基因人类表皮生长因子受体2（HER-2）阳性炎性乳腺癌是指HER-2过表达或扩增的炎性乳腺癌。临床上以乳房表面皮肤呈炎性改变而没有溃疡形成、局部及全身快速进展为特点,表现出更高的侵袭性。尽管炎性乳腺癌预后差,但新辅助化疗、手术及放疗等多学科综合治疗,尤其是分子靶向治疗显著改变了本病的自然进程。本文就近年来HER-2阳性炎性乳腺癌的分子靶向治疗进展作一综述。     

Safely promoting breast-conserving surgery and preventing early relapses with an aromatase inhibitor

Neoadjuvant therapy improves patient outcomes substantially by increasing the rate of breast-conserving surgery. Following primary surgery, women with hormone-sensitive early breast cancer remain at risk for loco-regional and systemic recurrence. The most common relapse event, distant metastases, is associated with the poorest outcomes. As a neoadjuvant therapy, anastrozole, letrozole, and exemestane have been investigated in phase 3 studies and have shown efficacy in this setting. All three aromatase inhibitors (AIs) significantly improved the rate of breast-conserving surgery. As initial adjuvant therapy, the third-generation AIs anastrozole and letrozole more effectively reduce recurrence risk compared with tamoxifen following surgery, especially in the first 2 years, when the risk is greatest. Tamoxifen, once the standard initial therapy, is associated with improved disease-free survival but may be more effective at reducing loco-regional recurrence than distant metastases. Initial adjuvant letrozole therapy has also shown a pronounced reduction in the risk of distant metastases early on in the course of therapy. If AIs are not used upfront, sequential use of exemestane or anastrozole following tamoxifen provides greater protection against relapse than continuing on tamoxifen. Side effects associated with estrogen deprivation of AIs are less serious than those of tamoxifen and are easily managed. Various molecular markers are under study as surrogates to predict response to neoadjuvant therapy, which may in turn predict responsiveness to adjuvant therapy. Surgeons treating breast cancer patients and prescribing endocrine therapy should be aware of all treatment strategies, including neoadjuvant and adjuvant hormonal therapy, and inform their patients of the benefits and the potential side effects. Early and long-term-risk reduction with AI treatment should be discussed with patients, as should the management of common AI-associated adverse events.