De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017

The 15th St. Gallen International Breast Cancer Conference 2017 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer. Treatments were assessed in light of their intensity, duration and side-effects, seeking where appropriate to escalate or de-escalate therapies based on likely benefits as predicted by tumor stage and tumor biology. The Panel favored several interventions that may reduce surgical morbidity, including acceptance of 2 mm margins for DCIS, the resection of residual cancer (but not baseline extent of cancer) in women undergoing neoadjuvant therapy, acceptance of sentinel node biopsy following neoadjuvant treatment of many patients, and the preference for neoadjuvant therapy in HER2 positive and triple-negative, stage II and III breast cancer. The Panel favored escalating radiation therapy with regional nodal irradiation in high-risk patients, while encouraging omission of boost in low-risk patients. The Panel endorsed gene expression signatures that permit avoidance of chemotherapy in many patients with ER positive breast cancer. For women with higher risk tumors, the Panel escalated recommendations for adjuvant endocrine treatment to include ovarian suppression in premenopausal women, and extended therapy for postmenopausal women. However, low-risk patients can avoid these treatments. Finally, the Panel recommended bisphosphonate use in postmenopausal women to prevent breast cancer recurrence. The Panel recognized that recommendations are not intended for all patients, but rather to address the clinical needs of the majority of common presentations. Individualization of adjuvant therapy means adjusting to the tumor characteristics, patient comorbidities and preferences, and managing constraints of treatment cost and access that may affect care in both the developed and developing world.     

Sequencing of endocrine therapies in breast cancer--integration of recent data

A wide range of endocrine therapies has demonstrated activity in the treatment of hormone receptor-positive metastatic breast cancer and sequential tumor responses to sequential hormonal therapies are common. However, the optimal sequence of the hormonal therapies has not yet been determined. The selection of endocrine therapies in women with hormone receptor-positive breast cancer is strongly influenced by the menopausal status of the patient. For premenopausal women, tamoxifen alone or combined with ovarian suppression using a luteinizing hormone-releasing hormone (LHRH) agonist - such as goserelin or leuprolide - is an appropriate first-line hormonal therapy. Ovarian ablation or megestrol acetate is an appropriate second-line hormonal therapy for premenopausal women treated with tamoxifen as first-line therapy, or ovarian ablation plus an aromatase inhibitor (AI) or megestrol acetate for women treated with first-line tamoxifen plus an LHRH agonist. For postmenopausal women, the non-steroidal AIs anastrozole and letrozole now represent the preferred first-line hormonal treatment for metastatic breast cancer, based upon both efficacy and toxicity considerations. For second-line therapy in postmenopausal women, a number of options now exist, including tamoxifen, the steroidal AI exemestane, and the new agent fulvestrant. Fulvestrant, a novel estrogen receptor (ER) antagonist that downregulates the ER and has no known agonist effects, has been demonstrated to be at least as effective as anastrozole in postmenopausal women whose tumors progress on tamoxifen. The establishment of the optimal sequence of the endocrine therapies should offer significant benefits to women with hormone-sensitive metastatic breast cancer.     

Systemic therapy for older women with breast cancer

Breast cancer is a common problem in older women. As the number of medical illnesses increases with age and the life expectancy decreases, the benefits of systemic therapy for women with breast cancer become questionable. All women over age 65 years are at high enough risk of breast cancer to consider the risk/benefit ratio of preventive therapy with tamoxifen (Nolvadex) or participation in the Study of Tamoxifen and Raloxifene (STAR) trial. Adjuvant chemotherapy and hormonal therapies for early breast cancer significantly improve disease-free and overall survival; recommendations for their use are based on risk of tumor recurrence. Use of tamoxifen in the adjuvant setting in women with receptor-positive tumors is a relatively simple decision in light of its favorable toxicity profile. The delivery of adjuvant chemotherapy is a more complicated decision, and the patient's wishes, estimated life expectancy, presence of comorbid conditions, and estimated benefit from treatment should be considered. The primary goal of the treatment of metastatic breast cancer is palliation. We discuss trials specific to older women and make appropriate treatment recommendations. Unfortunately, there is a paucity of data from clinical trials in women over age 70 years. However, because the clinical trial is the primary scientific mechanism for testing the efficacy of a treatment, every effort should be made to enter older women into treatment protocols.     

Changing Beliefs and Practices in Women With Breast Cancer in China

The trends of surgical therapy for breast cancer in China between 1999 and 2008 show persistent use of modified radical mastectomy and slow uptake of sentinel node mapping for women with early-stage breast cancer. Additional health care programs must be developed and implemented in China to promote awareness and a multidisciplinary approach to treating breast cancer, including adoption of screening mammography, breast-conserving surgery, and sentinel node mapping and biopsy.In this issue of The Oncologist, Dr. Qiao and colleagues report on the trends of surgical therapy for breast cancer in China between 1999 and 2008 [1]. Their data reflect the results of women treated for breast cancer in a single university hospital from each of the seven geographic regions in China. What is most striking about their report is the persistent use of modified radical mastectomy and slow uptake of sentinel node mapping for women with early-stage breast cancer. Equally striking is that the highest incidence of early breast cancer in China occurs at the age of 45 years, which is a full decade earlier than women in the U.S. There are many reasons for the delay in widespread adoption of breast-conserving surgical techniques in China. Reviews like this one shed light on important factors that will help shape progress in this area and emphasize the need for urgent health care redesign in the treatment of breast cancer in China.In 1985, the first randomized trial demonstrating equivalent efficacy between breast-conserving surgery (BCS) and mastectomy was published in the U.S. [2]. Between 1985 and 1989, approximately 35% of women with stage I and 19% with stage II breast cancer were treated with BCS. In 1990, the National Institutes of Health consensus development conference published recommendations for using BCS for the treatment of early-stage breast cancer [3]. Within 5 years, the proportion of women undergoing BCS had increased to 60% for stage I and 39% for stage II breast cancer patients. Over the past decade, the proportion of women with early-stage disease undergoing BCS has remained fairly stable at approximately 70%. Recently, however, the proportion of mastectomies done for early-stage breast cancer appears to be increasing. The reasons behind this shift are multifactorial but largely due to improvements in reconstruction techniques and options that avoid long-term surveillance and prolonged years of endocrine therapy. Changes in practice occur faster today than in the past because of advances in technology, global dissemination of information, and public awareness. Physicians and patients have similar access to information regarding new techniques for cancer diagnoses and treatments. An increasing number of productive women in China are affected by this disease each year. With the assistance of modern technology and more health care resources, women in China will hopefully soon be able to look forward to a change in the perception of what breast cancer surgery should look like in the 21st century and similarly realize that they can expect a good outcome and future after breast cancer.Measuring quality of breast cancer care by the percentage of BCS may not be an accurate assessment of the landscape in China. Surgery remains a vital component of breast cancer care, yet improved survival and prevention of a second breast cancer are now closely linked to screening and the benefits of adjuvant therapies including radiation, chemotherapy, and endocrine therapy [4]. Treating breast cancer in the U.S. and in many other Western countries is done in a multidisciplinary setting. Incorporating adjuvant therapies into the treatment algorithm comes at a cost not only to the health care system but also to the patient. Adapting the multidisciplinary approach used in the U.S. to treat breast cancer in China will not only involve changing surgical options but also having adjuvant therapy resources available and a willingness to accept the loss of productivity during treatment and in some cases long term.Another milestone in the surgical practice for breast cancer has been the impact that sentinel node mapping and biopsy (SNB) has had on reducing morbidity. Sentinel node mapping in breast cancer began in 1991, and the first article was published by Giuliano et al. in 1994 [5]. Numerous studies have validated the technique, and there is general acceptance for the use of sentinel node biopsy in early-stage breast cancer to select patients with occult lymph node metastases who may benefit from further regional or systemic therapy. SNB reduces the morbidity of treatment and improves quality of life following treatment without compromising local control and the accuracy of staging. In developing countries, there are barriers to using this technique. Availability of the contrast materials necessary to perform the procedure and pathologists to interpret the results limit its use in areas where there are competing economic issues and lack of resources. The results of a SNB generally help physicians make decisions about systemic therapy and aid in the planning of appropriate radiation therapy fields of treatment. Having this information may be somewhat irrelevant if these adjuvant therapies are not available. On the other hand, there is a fairly widespread consensus that a full axillary dissection is unnecessary in approximately 80% of women with early-stage breast cancer because their nodes are not involved. Once patient advocates in the U.S. learned about the reduced morbidity associated with SNB they helped tremendously to move this part of the field forward by querying their surgeons about the technique. The health care system in China needs to embrace SNB by making resources and training available for physicians to learn this technique. Increasing public awareness of this option may also help to encourage surgeons to incorporate this technique into their practices.Breast cancer is the most commonly diagnosed cancer in woman worldwide. The breast cancer incidence rate in China has steadily increased over the past 20 years and is projected to double within the next decade. This increase in incidence parallels that in the U.S., which increased slowly between 1940 and 1980, sharply increased in the early 1980s because of wider use of screening mammography, then stabilized in the 1990s, and began to decrease in 2000 after the decline in use of hormone replacement therapy. The incidence of breast cancer in the U.S. has remained stable since 2007, at approximately 124 cases per 100,000 women. Most importantly, however, mortality from breast cancer in the U.S. has decreased since 1975 because of the contributions of regular screening mammography and adjuvant therapy. The increasing incidence and the simultaneously increasing mortality rates associated with breast cancer in China should be a stimulus to increase the pace of change.Breast cancer screening has been shown to reduce rates of breast cancer mortality. A meta-analysis of 13 randomized trials found a 26% reduction in the relative risk of breast-cancer related mortality when women aged 50–74 years received screening mammography [6]. Other reviews have estimated a relative risk reduction of only 15%. It is likely that adoption of screening mammography in China would initially result in a shift toward earlier stage diagnoses of breast cancer and a drop in mortality. However, it is possible that the benefit may be blunted compared with its benefit in the U.S. because of the earlier age of diagnosis and the accompanying increased breast density which reduces the sensitivity of mammography. It may be that breast ultrasound is ultimately a better imaging tool for screening premenopausal women in China. The health care system in China will hopefully embrace the benefits of what technology can offer to increase awareness among its citizens regarding the incidence of breast cancer, the availability and recommendations for screening for breast cancer, and the curability of this disease if identified at an early stage.Earlier diagnosis will lead to increased survival and should be the highest priority in any health care system. The second priority in breast cancer care should be reducing the extent of surgery as long as there is access to adjuvant therapies that maintain the same level of treatment efficiency and long-term survival. In Western countries, the percentage of patients surviving at least 5 years after diagnosis and treatment is more than 90%. As life expectancy worldwide increases, our treatments for breast cancer need to be long lasting and impose less morbidity. Individual choices regarding the extent of treatment may depend upon education level, availability to centers with radiation, adjuvant therapy options, competing obstacles in life, and family structure. Patient preference may also vary based upon the physician-patient interaction, which is an increasingly complicated and evolving dynamic that we all need to embrace. Recognizing that it is possible to save more women’s lives and simultaneously minimize the morbidity of treatment will hopefully continue to stimulate those in the Chinese health care system to develop and implement additional health care programs to promote awareness, screening, and a multidisciplinary approach to treating breast cancer.     

The Role of Surgery in the Treatment of Older Women with Breast Cancer

A significant proportion of women diagnosed with breast cancer are over the age of 70 years and there is evidence that these patients frequently do not receive standard treatments, including surgical procedures and adjuvant therapies, which would be routine practice in younger age groups. The factors underlying this may include the physiological effects of ageing, differences in the biology and stage of the tumour at presentation, patient co-morbidities and patient and clinician preferences. The interaction of all these factors needs to be considered when individualising treatment plans for patients. For some patients this will need to be undertaken in the context of an extended multidisciplinary team setting with additional input from geriatricians, in addition to surgeons and oncologists, in defining a treatment plan. Little is known about the preferences of older patients in their choice of surgical treatment for breast cancer and further research is required to increase the evidence base for the rational management of older women with breast cancer.     

Screening and diagnosis of breast cancer in augmented women

Cosmetic breast enlargement surgery has become common in Japan. There are some reports suggesting that implants can interfere with mammography (MMG) and may lead to delayed breast cancer diagnosis, even when implant-displaced MMG (Eklund technique) is performed. Screening MMG was recommended in a notification issued by the Japanese Ministry of Health, Labor and Welfare in 1999, and MMG is just coming into widespread use in Japanese breast cancer screening. Recent reports suggest that screening MMG may not be appropriate in augmented women, but breast self-examination may be effective in these women. Ultrasonography (US) may be useful in screening augmented women without risk of rupturing the implant. In appropriate cases, magnetic resonance imaging should be considered as an adjunct to MMG and US. The question of whether augmented women should not undergo core needle biopsy because of the possibility of damage to the implant should be considered. This review discusses diagnostic methods for augmented women and suggests the optimal screening method for augmented women. The challenge of the screening and diagnosis of breast cancer in augmented women is important in order to detect more of their cancer at a preclinical stage, because we can expect to see breast cancer in augmented women with increasing frequency over the next decade.     

Side effects, quality-of-life issues, and trade-offs: the patient perspective.

Increasingly effective adjuvant treatments of invasive breast cancer and their widespread use have improved survival rates. Given the timing required by its use, adjuvant therapy requires the patient to absorb complex medical data and make challenging trade-offs shortly after initial diagnosis. However, many women are unprepared or unable to optimize adjuvant treatment decisions while experiencing the shock and dismay that often follow the confirmation of an invasive breast cancer diagnosis. Each woman needs to know the facts and circumstances of her own case and to fully understand the benefits and risks of adjuvant therapy. Only then can she, with her medical team, choose those therapies that will maximize her benefit as a patient and as a survivor in all aspects of her life, over both the short and longer term. To help the patient accomplish these goals, individualized practical knowledge that complements population-based advances in survival is critically needed. Considerable focus, study, and cross-disciplinary collaboration will be required to compile successful, integrated approaches to adjuvant therapy that reflect varying patient contexts and concerns. Other crucial ingredients are the investment of resources in recently established research fields (such as the tracking of psychosocial outcomes and delayed morbidity) and informed guidance from patient advocates. To accelerate patient-centered progress in adjuvant therapy for breast cancer, areas that need attention include targeted public education programs; patient information and informatics; treatment selection and decision-making tools; and interventions and therapies to improve quality of life for patients, survivors, and their families. Underlying all of these efforts should be culturally competent, multigenerational approaches to communicating effectively with diverse patients and family members in multiple clinical and community settings.     

Fertility preservation in breast cancer patients

Systemic therapies have been shown to effectively improve prognosis in patients with breast cancer. However, such therapies also become increasingly harmful as their duration increases, and they have adverse effects on fertility and ovarian function. Fertility preservation (FP) is important in young adult cancer survivors who may wish to have children. In Japan, some cancer societies recommend that the potentially serious effects of systemic therapy on ovarian function should be explained to women with cancer, and they should be encouraged to undergo FP prior to commencing treatment. Still, as there are no official guidelines, many oncologists lack the required knowledge and mind-set to advise young breast cancer patients on fertility issues. Counseling of patients and their families might improve their understanding about the influence of such treatment on fertility and ensure effective FP. There are several FP methods that can be selected before beginning treatment, and these methods have both advantages and disadvantages. Young adults with breast cancer who want to bear children in the future must be provided with FP counseling, in addition to advice about breast cancer treatment and prognosis.     

Management of HER-2/neu-positive metastatic breast cancer

We reviewed therapies for the management of HER2-overexpressing metastatic breast cancer. HER2-overexpressing breast cancers have a distinctive molecular signal and distinctive clinical characteristics. They are associated with an adverse prognosis, relative resistance to certain types of therapies (i.e. tamoxifen), and responsiveness to anthracyclines and taxanes. Anti-HER2 therapies such as trastuzumab and lapatinib have revolutionised the treatment of breast cancer and can dramatically improve outcomes in women with HER2-overexpressing metastatic breast cancer. Response to these targeted agents is improved when used in combination with cytotoxic agents such as anthracyclines and taxanes. However, there is an approximate 13% (taxanes) to 27% (conventional anthracyclines) risk of cardiotoxicity with these combinations. The novel anthracycline, pegylated liposomal doxorubicin, shows efficacy similar to that of conventional doxorubicin and may offer significantly less cardiotoxicity; this should be confirmed in phase III clinical trials. Lapatinib is an oral small molecule targeting HER2 with promising antitumour activity in the metastatic setting and a potential for reduced cardiotoxicity as compared with trastuzumab. Neoadjuvant as well adjuvant trials involving lapatinib, trastuzumab or their combination have started recrutiment worldwide.     

Treatment of estrogen deficiency symptoms in women surviving breast cancer. Part 1: Defining the problem. Proceedings of a conference held at the Boar's Head Inn Charlottesville, Virginia. September 21-23, 1997

There are several million breast cancer survivors worldwide. In the United States, 180,000 women were diagnosed with breast cancer in 1997, and approximately 97,000 of these women have an extremely low chance of suffering a recurrence of their cancer. With an average age at diagnosis of 60 years and a 25-year expected duration of survival, the current number of breast cancer survivors in the United States may approach 2.5 million women. Since breast cancer is now being detected at an earlier stage than previously and since adjuvant chemotherapy may cause ovarian failure, an increasing number of women are becoming postmenopausal at a younger age after breast cancer treatment. This conference was convened in September 1997 to consider how menopausal breast cancer survivors should be treated at the present time and what future studies are needed to develop improved therapeutic strategies. A total of 47 breast cancer experts and 13 patient advocates participated. The proceedings of the conference will be published in six installments in successive issues of ONCOLOGY. This first part defines the problem and explores its magnitude and ramifications for patient management.     

Moving to a High-tech Approach to the Irradiation of Early Breast Cancer: Is It Possible to Balance Efficacy,Morbidity and Resource Use?

There is substantial evidence documenting the potential morbidity associated with radiotherapy in early breast cancer. An appraisal of current standard radiation practice is therefore necessary, given that women are surviving longer, have an improved quality of life, and are overcoming subsequent side-effects caused by postoperative irradiation. New technology allows the application of more complex approaches. This discussion paper considers some of the benefits of the widespread use of new complex approaches, such as intensity-modulated radiotherapy (IMRT) in the light of staffing and equipment shortfalls, and possible consequences on waiting times for treatment. The discussion is considered under the following themes: (1) which women with breast cancer benefit from complex treatment approaches? (2) What is the role of treatment accuracy in limiting morbidity? And (3) what is the potential effect of complex breast irradiation approaches on service delivery? In the UK, and globally, many departments are struggling to meet waiting-time guidelines. The use of more complex approaches for breast irradiation may increase this difficulty. However, a number of simple technical changes can be used to enhance efficacy and reduce levels of normal tissue morbidity. A sub-set of women who are at greatest risk from normal tissue morbidity or reduced cosmesis should be accurately defined in order to allow departments to plan their treatment strategies with optimal use of resources.     

Does hormone therapy for the treatment of breast cancer have a detrimental effect on memory and cognition? A pilot study

This pilot study examines whether hormone therapy for breast cancer affects cognition. Patients participating in a randomised trial of anastrozole, tamoxifen alone or combined (ATAC) (n=94) and a group of women without breast cancer (n=35) completed a battery of neuropsychological measures. Compared with the control group, the patients were impaired on a processing speed task (p=0.032) and on a measure of immediate verbal memory (p=0.026) after controlling for the use of hormone replacement therapy in both groups. Patient group performance was not significantly related to length of treatment or measures of psychological morbidity. The results showed specific impairments in processing speed and verbal memory in women receiving hormonal therapy for the treatment of breast cancer. Verbal memory may be especially sensitive to changes in oestrogen levels, a finding commonly reported in studies of hormone replacement therapy in healthy women. In view of the increased use of hormone therapies in an adjuvant and preventative setting their impact on cognitive functioning should be investigated more thoroughly.     

Breast cancer in older patients

Breast cancer is a common problem and a major health concern in our growing geriatric population. Older breast cancer patients are at risk for less than standard management, the appropriateness of which is difficult to discern. Breast tumors tend to have less aggressive characteristics. In addition, planning therapy is not always straightforward because older patients may present with comorbid illnesses and frailty that limit therapeutic choices. Standard management approaches should always be considered first. Here, we outline some data supporting standard treatment for breast cancer in older women. We also describe other options that can be considered in circumstances when the standard treatment is not possible. For instance, primary treatment with tamoxifen or an aromatase inhibitor is justifiable in a patient who is unfit for surgery and axillary dissection may be unnecessary in a patient who is obviously unfit for adjuvant chemotherapy. Adjuvant therapies should be considered, weighing risks and benefits for each patient, though the threshold for using chemotherapy may be higher. The goals in treating metastatic breast cancer in an older patient are not different than for younger patients.     

Adverse bone effects during pharmacological breast cancer therapy

The improved survival and cure rate of breast cancer patients leads to increased diagnosis of later occurring side effects to therapy such as osteoporosis. Conventional chemotherapies such as CMF and CEF are known to induce premature menopause, which increases bone loss but these therapies have additional detrimental effects on bone. The loss in bone mass during chemotherapy is substantial and may lead to increased fracture risk. The influence of taxanes on bone is less well known. Whereas tamoxifen has a slight protective effect on bone loss the opposite is true for aromatase inhibitors. Adverse effect reportings show, that adjuvant treatment with aromatase inhibitors in postmenopausal women increases the risk of clinical fractures as compared to tamoxifen. The Danish Bone Society suggests that all women with operable breast cancer have their fracture risk evaluated including a BMD measurement prior to initiation of adjuvant aromatase inhibitor therapy as a part of the standard examination program. If osteoporosis is diagnosed, anti-osteoporosis therapies should be considered. Moreover, all women undergoing adjuvant chemotherapy and endocrine therapy should be informed of the risk of bone loss and should receive life style advice of how to preserve bone. Adjuvant regimens in breast cancer patients improve survival and cure rates. Therefore it is preferable to use such therapies although they increase risk of side effects such as osteoporosis.     

Skeletal health in postmenopausal survivors of early breast cancer

Estrogen plays an important role in the skeletal health of all women. Many therapies used in the treatment of breast cancer reduce estrogen levels and have the potential to affect bone negatively by increasing the risk of osteoporosis and associated bone fractures. The long-term effects of systemic endocrine therapy on bone, therefore, are an important consideration in the adjuvant setting. Tamoxifen has been shown to have a moderate protective effect on postmenopausal bone due to its partial estrogen agonist activity; however, its long-term use is potentially associated with negative side effects, such as an increased risk of thromboembolic disease and endometrial cancer. Newer agents, the third-generation aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, for example, do not possess estrogen agonist effects and have improved breast cancer outcomes when compared to the standard 5 years of tamoxifen. However, patients treated with adjuvant AIs have been shown to have an increased incidence of osteoporosis and osteoporotic fractures. In order to select the optimal adjuvant therapy for each patient, it is important to assess the overall risk:benefit ratio for each endocrine strategy. All postmenopausal women should follow published guidelines to assess the risk of osteoporosis and, where appropriate, they should receive bone mineral density monitoring. Postmenopausal women with breast cancer who are at increased risk of osteoporotic fracture should be identified and managed with appropriate nonpharmacologic and pharmacologic measures.     

Treatment of estrogen deficiency symptoms in women surviving breast cancer. Part 2: Hormone replacement therapy and breast cancer

There are several million breast cancer survivors worldwide. In the United States, 180,000 women were diagnosed with breast cancer in 1997, and approximately 97,000 of these women have an extremely low chance of suffering a recurrence of their cancer. With an average age at diagnosis of 60 years and a 25-year expected duration of survival, the current number of breast cancer survivors in the United States may approach 2.5 million women. Since breast cancer is now being detected at an earlier stage than previously and since adjuvant chemotherapy may cause ovarian failure, an increasing number of women are becoming postmenopausal at a younger age after breast cancer treatment. This conference was convened in September 1997 to consider how menopausal breast cancer survivors should be treated at the present time and what future studies are needed to develop improved therapeutic strategies. A total of 59 breast cancer experts and patient advocates participated. The proceedings of the conference will be published in six installments in successive issues of ONCOLOGY. The first part, published last month, defined the problem and explored its magnitude and ramifications for patient management. This second part focuses on the benefits and risks of hormone replacement therapy (HRT) in patients with breast cancer.     

Estimating the benefits of therapy for early-stage breast cancer: the St. Gallen International Consensus Guidelines for the primary therapy of early breast cancer 2019

BackgroundThe 16th St. Gallen International Breast Cancer Conference 2019 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer.DesignTreatments were assessed in light of their intensity, duration and side-effects, estimating the magnitude of clinical benefit according to stage and biology of the disease. The Panel acknowledged that for many patients, the impact of adjuvant therapy or the adherence to specific guidelines may have modest impact on the risk of breast cancer recurrence or overall survival. For that reason, the Panel explicitly encouraged clinicians and patients to routinely discuss the magnitude of benefit for interventions as part of the development of the treatment plan.ResultsThe guidelines focus on common ductal and lobular breast cancer histologies arising in generally healthy women. Special breast cancer histologies may need different considerations, as do individual patients with other substantial health considerations. The panelists’ opinions reflect different interpretation of available data and expert opinion where is lack of evidence and sociocultural factors in their environment such as availability of and access to medical service, economic resources and reimbursement issues. Panelists encourage patient participation in well-designed clinical studies whenever available.ConclusionsWith these caveats in mind, the St. Gallen Consensus Conference seeks to provide guidance to clinicians on appropriate treatments for early-stage breast cancer and guidance for weighing the realistic tradeoffs between treatment and toxicity so that patients and clinical teams can make well-informed decisions on the basis of an honest reckoning of the magnitude of clinical benefit.     

Current targeted therapies in breast cancer: clinical applications in the elderly woman

The incidence of breast cancer is two to three times higher in women aged ≥65 years than in the whole population, whereas their mortality rate is threefold to fourfold higher. Targeted therapies allow significantly longer disease-free survival times. Nevertheless, in an elderly population, these treatments need to be prescribed with caution. This paper reviews the treatments of breast cancer in the elderly, and the issues of targeted therapies and their toxicities. Patients with human epidermal growth factor receptor (HER)-2(+) breast cancer benefit from trastuzumab; although cardiotoxic effects are observed in <5% of patients when given alone, they affect ~25% of patients when combined with anthracyclines. Bevacizumab leads to a longer progression-free survival time and lower risk for progression in patients with metastatic breast cancer when added to paclitaxel or docetaxel. Although generally well tolerated, it is associated with a higher risk for arterial thromboembolism and hypertension. Lapatinib is approved for the treatment of advanced or metastatic breast cancer in patients not responding to trastuzumab, combined with capecitabine chemotherapy. The most frequent side effects concern the gastrointestinal system and dermatologic symptoms. The life expectancy of breast cancer patients should be taken into account to determine the appropriateness of treatments. The quality of life of elderly cancer patients must be assessed with an appropriate tool. Older patients exhibit greater vulnerability, suggesting identification and exclusion of patients at high cardiac risk. Future recommendations for the treatment of elderly women with breast cancer should include a multidisciplinary approach and a global geriatric assessment before treatment with anti-HER-2 therapy or bevacizumab.     

Aromatase inhibitors in the treatment of early and advanced breast cancer

The third generation aromatase inhibitors anastrozole, exemestane, and letrozole have been compared with tamoxifen and other endocrine therapies in several studies in early and advanced breast cancer. These studies are reviewed in this report. Based on the available evidence, the panel recommends that adjuvant treatment with tamoxifen for 5 years should no longer be considered as the sole standard but that a third-generation aromatase inhibitor should be used either alone or in a sequence with tamoxifen in the adjuvant treatment of postmenopausal women with hormone-receptor-positive breast cancer. Third generation aromatase inhibitors may be considered as the first line therapy of hormone-receptor-positive advanced breast cancer in postmenopausal women, and they may also be used for preoperative therapy of breast cancer.     

Should bisphosphonates be utilized in the adjuvant setting for breast cancer?

Adjuvant therapies for early breast cancer are associated with substantial decreases in bone mineral density. Bisphosphonates are antiresorptive agents that have an established role in preventing skeletal morbidity in patients with bone metastases and in the treatment of osteoporosis. Recently, several trials have demonstrated the efficacy of bone-directed agents for prevention of cancer treatment-induced bone loss in both premenopausal and postmenopausal women with early stage breast cancer. Moreover, it is now becoming evident that bisphosphonates may also exert anticancer effects in the adjuvant setting. For example, long-term follow-up of a study in patients with bone marrow micrometastases from breast cancer revealed overall survival benefits for clodronate versus placebo, and an ongoing large trial may provide further insights. Addition of twice-yearly zoledronic acid to standard adjuvant endocrine therapy significantly improved disease-free survival and decreased disease recurrence compared with standard therapy alone in 3 clinical trials involving nearly 3,500 patients with stage I-IIIA breast cancer, and monthly zoledronic acid during neoadjuvant therapy decreased residual tumor volume and improved pathologic response in patients with stage II/III breast cancer. Overall, a large and growing body of evidence suggests the potential adjuvant benefits of bisphosphonates in early breast cancer.