Breast Cancer

Adjuvant hormonal deprivation therapy is often administered long-term to patients with hormone receptor–positive cancers for primary prevention of breast cancer and secondary prevention of a recurrence.[1,2] This treatment modality is of particular importance to the elderly for two reasons: 1) the incidence of hormone-sensitive cancers (eg, prostate cancer and breast cancer) increases with age,[3] and 2) the systemic treatment regimens for elderly patients with hormone-responsive cancers are often limited to long-term hormonal deprivation therapy (HDT), most commonly androgen deprivation therapy for prostate cancer and aromatase inhibitor therapy for breast cancer, with chemotherapy often omitted.[2,4]

The incidence of metabolic syndrome is rapidly increasing. Metabolic syndrome is associated with elevated morbidity and mortality secondary to cardiovascular disease, insulin resistance, and hepatic dysfunction. A body of evidence has already implicated metabolic syndrome as a cancer risk factor; emerging evidence now suggests that cancer survivors themselves may be at risk for developing metabolic syndrome as a result of their anti-cancer therapy. Treatment of both breast cancer and prostate cancer often involves hormone-modifying agents that have been linked to features of metabolic syndrome. Androgen suppression in men with prostate cancer is associated with dyslipidemia, increasing risk of cardiovascular disease, and insulin resistance. Anti-estrogen therapy in women with breast cancer can affect lipid profiles, cardiovascular risk, and liver function. Similar findings have been noted in men with testicular cancer treated with chemotherapy. In addition, several emerging therapies, including mammalian target of rapamycin (mTOR) inhibitors and targeted kinase inhibitors, are increasingly associated with some features of metabolic syndrome. As the number of cancer survivors continues to grow, consideration of these factors and of the risk of metabolic syndrome will become increasingly important when choosing between therapy options and managing long-term follow-up.

Each year in the United States, more than 200,000 women are diagnosed with breast cancer, and 40,000 women die of the disease.[1] Approximately two-thirds of breast cancers are hormone receptor–positive, and medications that suppress estrogen are the cornerstone of adjuvant therapy for these tumors. Tamoxifen, a selective estrogen receptor modulator, was the first agent developed for this purpose and is still used widely in premenopausal women. Aromatase inhibitors (AIs), which prevent peripheral conversion of adrenal androgens into estrogen, have largely become the agents of choice for postmenopausal women. Current guidelines recommend that all postmenopausal women with hormone receptor–positive early-stage breast cancer who do not have a contraindication to AIs be treated with one of these agents, either as primary therapy or after 2 to 5 years of tamoxifen treatment as part of a cross-over strategy.[2] These recommendations are based on five large adjuvant trials that demonstrated a 3% to 4% absolute reduction in subsequent breast cancer events in patients who received an AI as part of adjuvant breast cancer treatment compared with patients treated with 5 years of tamoxifen alone.[3-7] However, it is notable that despite the lower rates of recurrence in these trials in the patients who received AIs, most studies have not demonstrated a survival advantage for AIs.

An FDA advisory panel has recommended that bevacizumab (Avastin) no longer be approved for use in patients with breast cancer.

Cancer investigators at Vanderbilt-Ingram Cancer Center in Nashville, Tenn., have confirmed that the PI3-kinase (PI3K) pathway offers a promising therapeutic target in patients who develop resistance to standard endrocine therapies.

Patient preference needs to be weighed against overall societal benefits.

Advances in our understanding of the underlying molecular mechanisms in the development of breast cancer have been at the forefront of recent clinical research. Many of the ASCO 2010’s hottest sessions featured clinical trials that looked at combination therapies with targeted agents as well as clinical improvements in standard-of-care in breast cancer.

Postmastectomy radiation therapy increased five-year overall survival by almost 50% and reduced recurrence risk by nearly 30%, according to a study in the International Journal of Radiation Oncology, Biology, Physics.

If approved, oncologists will have a new therapeutic option with proven benefits, acceptable toxicity, said EMBRACE trial leader.

Advances in our understanding of the underlying molecular mechanisms in the development of breast cancer have been at the forefront of recent clinical research. Many of the ASCO 2010’s hottest sessions featured clinical trials that looked at combination therapies with targeted agents as well as clinical improvements in standard-of-care in breast cancer.

Modifiable-risk biomarkers are increasingly being used in early-phase research to guide larger prevention trials.

Breast cancer is predominantly a disease of older women. Many of these older patients with breast cancer have low-risk disease owing to low proliferation indices, positive hormone receptors, node-negativity, or p53-negative and HER-2 (human epidermal growth factor 2)-negative tumors.[1,2] They do well without chemotherapy and will receive adjuvant hormonal therapy with tamoxifen or an aromatase inhibitor. Yet there are older women who do not have these favorable tumor characteristics and so are potential candidates for chemotherapy. The review by Muss points out this issue, highlighting benefits of chemotherapy and describing appropriate treatment regimens for these patients.

Although increasing age is the major risk factor for breast cancer incidence and mortality, when adjusted for disease stage, breast cancer mortality is similar among younger vs older patients. Importantly, about 90% of older women with breast cancer present with early-stage disease. The biologic characteristics of breast tumors in older patients suggest they would derive benefit from adjuvant therapy, particularly endocrine therapy, but older women are still frequently undertreated, resulting in poorer survival. Studies suggest that focusing on comorbidity rather than “chronologic age” as a surrogate for life-expectancy is a key aspect of adjuvant decision-making for older patients. Morbidity and mortality from cancer in vulnerable patients with poorer health can be accurately predicted by the Comprehensive Geriatric Assessment (CGA), which evaluates comorbidities, functional status, cognition, social support, psychological state, nutritional status, and polypharmacy. Use of the CGA and newer versions of this tool can lead to interventions that maintain function and improve quality of life in older patients with breast cancer.

Dr. Hy Muss is a well recognized expert in the treatment of elderly women with breast cancer, and his article “Adjuvant Chemotherapy of Breast Cancer in the Older Woman” is an extremely important addition to the limited existing literature on this topic. As he points out, nearly half of all breast cancer diagnoses occur in women over 65 years of age. As the total number of women in that demographic increases with the aging of our population, medical oncologists will be faced with a growing number of elderly breast cancer patients, for whom evidence-based recommendations on treatment are needed. As any medical oncologist who sits face-to-face with these older women knows, it is not acceptable to simply tell the patient that there are inadequate data to guide recommendations for adjuvant chemotherapy in her age group, though this is what the EBCTCG (Early Breast Cancer Trialists Collaborative Group) overview has concluded.

There’s no shortage of controversy when it comes to mammography-based breast cancer screening.

Whole-body MRI should be the go-to imaging modality for detecting bone metastases in asymptomatic patients.

Opening of the Maggie Daley Center for Women’s Cancer Care at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

Tests carry a significant price tag, but reduction in chemotherapy use is potentially cost-saving.

Bone health is a critical issue in the management of women with breast cancer. Many women who develop breast cancer are postmenopausal, which already predisposes them to osteoporosis. Systemic treatments for breast cancer, including chemotherapy and endocrine therapy, decrease circulating levels of estrogen in both pre- and postmenopausal women, further accelerating the natural process of bone loss. The primary concern in breast cancer patients is that this accelerated bone loss, known as cancer treatment–induced bone loss (CTIBL), will lead to an increase in fractures, chronic pain, and loss of mobility. Bisphosphonates are highly effective at slowing the rate of bone loss in postmenopausal women with osteoporosis and at preventing skeletal-related events in women with metastatic breast cancer. Many studies are now focusing on the role of bisphosphonates in preventing CTIBL in the adjuvant setting. Both oral and intravenous bisphosphonates have shown promising activity in preventing CTIBL in patients receiving chemotherapy or hormonal therapy. In addition, emerging data indicate that the use of bisphosphonates in the adjuvant setting may prevent disease recurrence and prolong survival. Data from a number of ongoing trials will further elucidate the role of bisphosphonates in the adjuvant setting over the next few years.

A majority of the more than 190,000 women diagnosed with breast cancer each year in the US[1] will receive some form of adjuvant therapy. Many breast cancer treatments cause decreases in circulating estrogen levels, which in turn can have a significant effect on bone mineral density; this condition is known as cancer treatment-induced bone loss (CTIBL). In this issue of ONCOLOGY, Reeder and Brufsky review the role of bisphosphonates in the setting of adjuvant breast cancer treatment. Both oral and intravenous bisphosphonates are effective in the prevention and treatment of CTIBL, and emerging data suggest that adjuvant bisphosphonate therapy may also affect breast cancer recurrence and survival. In considering the role of these medicines in early stage breast cancer, however, a number of important questions remain.

Breast cancer is the most common noncutaneous cancer among women.[1] In 2009, an estimated 190,000 new cases occurred in the US. The 5-year survival rate for early-stage breast cancer has improved from approximately 63% in the early 1960s to almost 90% today, mainly as a result of early detection and treatment.[2] The improvement in survival from breast cancer treatments, however, which include chemotherapy, endocrine therapy, and/or ovarian ablation, does not come without the cost of potentially significant effects on bone mineral density (BMD).[3-5] The risk of having low bone mass increases significantly with age, as does the risk of developing breast cancer; consequently, the two diagnoses often overlap in the same individual. Additionally, women with breast cancer may be at increased risk for osteoporosis due to the effect on bone of certain anticancer therapies. Hence, some women with breast cancer may be at increased risk of osteoporosis.

The I-SPY 2 breast cancer trial features a novel design of uninterrupted enrollment and patient stratification using biomarkers in order to target therapy.

Trastuzumab (Herceptin) has dramatically changed the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer.

This review explores the use of several such agents, including lapatinib (Tykerb), HSP90 inhibitors, T-DM1, and other tyrosine kinase inhibitors. Emerging data from trials of these agents indicate that the HER2 pathway remains a valid therapeutic target following disease progression on trastuzumab.

An increasing number of women diagnosed with breast cancer chose to undergo contralateral prophylactic mastectomy, but this option only showed a real survival benefit in women who met certain criteria in terms of age, disease stage, and disease status.

The low-cost imaging technique has value for determining the relative aggressiveness of inflammatory and advanced disease.

While optimal adjuvant hormonal therapies for premenopausal women with operable breast cancer have yet to be defined, discussions and reviews of the state of the art and “areas of confusion” often fail to consider developments that are germane to keeping evidence-based clinical practice truly up-to-date.

The article “Adjuvant Hormonal Therapy in Premenopausal Women With Operable Breast Cancer: Not-So-Peripheral Perspectives” by Richard Love, published in this issue of ONCOLOGY,

Research and development of adjuvant therapies for premenopausal women with endocrine-responsive breast cancer is unfortunately lacking.

After malignancies of the skin, breast cancer is the most common cancer