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Breast imaging plays an important role in screening for breast cancer, classifying and sampling nonpalpable breast abnormalities, and defining the extent of breast tumors. Randomized clinical trials and meta-analyses have demonstrated lower mortality rates in women who undergo mammographic screening than in unscreened controls. In the past decade, there have been notable improvements in mammographic image quality and positioning. In breast conservation therapy, mammography is used to define the extent of malignancy before definitive breast-conserving surgery and to monitor the breast after surgery and radiation therapy. The use of stereotactic core needle biopsy has resulted in a decrease in the number of excisional biopsies performed. Mammography is also used to guide needle localizations, most of which, in our practice, are performed to help guide excision of known cancers. Magnetic resonance imaging shows great promise in detecting mammographically occult breast cancers and defining the extent of malignant disease. Magnetic resonance imaging-guided needle localization and core needle biopsy techniques have been developed to complement the increased utilization of magnetic resonance imaging in breast cancer staging. Technetium Tc 99 m sestamibi imaging has proven to be reasonably accurate in the evaluation of palpable breast lesions but is thought to have limited utility in the evaluation of nonpalpable breast lesions. Digital mammography systems offer opportunities for postprocessing and reconfiguring of the original data. [ABSTRACT FROM AUTHOR]

Hereditary predisposition to breast cancer accounts for approximately 5-10% of all breast cancers. The primary syndrome associated with an increased risk of breast cancer is hereditary breast and ovarian cancer syndrome, which is caused by mutations in the BRCA1 and BRCA2 genes. However, there are other hereditary cancer syndromes associated with an increased risk of breast cancer, including Li-Fraumeni syndrome, Cowden disease, Peutz-Jeghers syndrome, hereditary diffuse gastric cancer, and ataxia-telangiectasia. Genetic counseling and testing is a key component in the identification of individuals affected by these hereditary breast cancer syndromes. Genetic counseling is the process of educating patients and their families about inherited cancer risks based on their personal and family history and discussing the benefits, risks, limitations, and possible results of genetic testing. Once individuals are identified as having a hereditary breast cancer syndrome, they can be more effectively counseled regarding specific screening and prevention modalities, including chemoprevention and prophylactic surgeries. [ABSTRACT FROM AUTHOR]

A number of studies surveying breast cancer survivors have documented the impact of breast cancer diagnosis and breast cancer treatment on sexual function, sexual feeling, and sexual self-image. Women with breast cancer may experience loss of sexual desire, decreased arousability, diminished orgasmic capacity, impaired vaginal physiology, depression, and a lessened sense of "femaleness." Untreated sexual problems negatively affect intimate relationships, self-confidence, and physical well-being. Addressing the issue of sexual function before cancer treatment begins alerts the patient to the clinician's interest in this aspect of survivorship and increases the chance that the patient will bring future sexual problems to the attention of the treatment team. Depending on the nature of the problem and the disease context, interventions are available for treatment of sexual problems in breast cancer survivors. These include vaginal moisturizers, lubricants, medications or psychological therapy to alleviate depression-related sexual dysfunction, and couples therapy to address sexual and more general issues. [ABSTRACT FROM AUTHOR]

Because of treatment with chemotherapy, women with a history of breast cancer are more likely to be exposed to estrogen deficiency and often experience estrogen deficiency for a longer duration than women in the general population. Estrogen deficiency can cause hot flashes, vasomotor instability, genitourinary atrophy, cardiovascular disease, and osteoporosis. Hormone replacement therapy (HRT) is effective in the prevention and treatment of vasomotor instability, genitourinary atrophy, and osteoporosis. However, there are concerns that HRT may increase the risk of coronary heart disease and stroke. In addition, because breast cancer is believed to be a hormonally responsive disease, HRT is considered contraindicated in women with a history of this disease. Numerous nonhormonal alternatives are available to manage the symptoms of estrogen deficiency in breast cancer survivors. Despite the general consensus that HRT is contraindicated in breast cancer survivors, preliminary evidence indicates that in carefully selected women successfully treated for localized breast cancer, HRT does not have a pronounced adverse effect on the rate of cancer recurrence and may be considered after appropriate patient counseling. Women diagnosed with breast cancer while receiving HRT have a better prognosis than do women diagnosed with breast cancer while not receiving HRT. [ABSTRACT FROM AUTHOR]

Breast cancer survivors often face physical and psychosocial impairments that can adversely affect their quality of life. Not only surgery but also radiation therapy and systemic therapy can lead to sequelae that necessitate a rehabilitation program. Among the most common sequelae of breast cancer treatment are shoulder dysfunction, pain, and lymphedema. A cancer rehabilitation team can help minimize long-term disability, thereby improving quality of life. After breast cancer surgery, early mobilization of the ipsilateral arm with supervision by a physical medicine and rehabilitation physician and physical therapists can accelerate return of range of motion, decrease pain, and reduce emotional trauma without increasing the risk of postsurgical complications. A multidisciplinary approach involving a surgical oncologist, medical oncologist, radiation oncologist, physician specializing in physical medicine and rehabilitation, physical therapist, and occupational therapist can optimize the management of lymphedema. Inpatient rehabilitation can improve function in patients with severe disability, especially patients with advance disease. [ABSTRACT FROM AUTHOR]

A number of special clinical situations can arise during the care of a patient with breast cancer, including pregnancy, leptomeningeal disease, epidural spinal cord compression, hypercalcemia, and second primary malignancy. For women diagnosed with breast cancer during pregnancy, modified radical mastectomy with axillary lymph node dissection has been the most common surgical intervention, although breast-conserving surgery may be an option. At M. D. Anderson Cancer Center, pregnant women with breastancer have been treated with relative safety during the second and third trimesters of pregnancy with combination chemotherapy consisting of 5-fluorouracil, doxorubicin, and cyclophosphamide, and there have been no significant short-term complications for the majority of children exposed to chemotherapy in utero. Leptomeningeal disease, a life-threatening complication of breast cancer even when treated, is diagnosed by analysis of the cerebrospinal fluid and gadolinium-enhanced magnetic resonance imaging. Treatment involves intrathecal chemotherapy via an Ommaya reservoir with agents such as methotrexate or sustained-release cytarabine and radiation therapy for focal areas of bulky disease. Epidural spinal cord compression is usually diagnosed with magnetic resonance imaging, and treatment consists of corticosteroids and radiation therapy or surgery with or without radiation therapy. The primary agents used in the treatment of hypercalcemia of malignancy are the bisphosphonates, particularly zoledronic acid. Patients with breast cancer are at risk for a second breast cancer, and those who are exposed to chemotherapy, hormonal therapy, radiation therapy, or a combination of these are at increased risk for other second primary malignancies, including lung cancer, myelodysplastic syndrome, acute myeloid leukemia, and endometrial cancer. Regular follow-up with thorough histories and physical examinations as well as yearly mammograms are important for the detection of second malignancies in patients with a breast cancer history. [ABSTRACT FROM AUTHOR]

Many patients with breast cancer experience gynecologic problems during or after breast cancer treatment. Some of these problems are caused by chemotherapy or hormonal therapy; others are caused by low estrogen levels resulting from chemotherapy, hormonal therapy, or prophylactic oophorectomy; and still others are unrelated to breast cancer or its treatment. Women who receive myelosuppressive chemotherapy are more likely to suffer vulval and vaginal infections as such chemotherapy can affect ovarian function and thus alter the vaginal ecosystem. Dyspareunia in patients with breast cancer may be due to loss of secretion of the secondary sexual glands, spasm of muscles around the vagina, or aggravation of psychosexual problems that existed before the breast cancer diagnosis. Low estrogen levels resulting from oophorectomy or medications that suppress ovarian function can exacerbate urinary incontinence. Patients taking tamoxifen for breast cancer prevention are at increased risk for endometrial carcinoma and require careful monitoring. The evaluation of abnormal vaginal bleeding, uterine or vaginal prolapse, and uterine or ovarian enlargement in breast cancer patients is similar to the evaluation of these problems in patients without breast cancer. Vaginal sonography and hysteroscopy are useful diagnostic tools in patients with vaginal bleeding or other pelvic symptoms. More and more women are asking gynecologists about prophylactic oophorectomy. This surgery may be appropriate in women with a genetic predisposition to ovarian cancer. [ABSTRACT FROM AUTHOR]

Endocrine therapy has dramatically improved outcomes in patients with hormone receptor—positive breast cancer and, more recently, has proved to be valuable in breast cancer prevention. Endocrine therapy results in palliation of disease in 50-60% of patients with hormone receptor—positive metastatic breast cancer. Alone or combined with chemotherapy, adjuvant endocrine therapy significantly reduces the risk of recurrence and has a favorable impact on survival in patients with hormone receptor— positive earlier-stage disease. While tamoxifen remains the standard adjuvant endocrine therapy for premenopausal patients, incorporation of aromatase inhibitors is now recommended in the adjuvant treatment of postmenopausal patients with hormone receptor—positive breast cancer. Recent findings demonstrating additional benefit with extended adjuvant endocrine therapy have generated excitement given the prolonged period during which patients are vulnerable to breast cancer recurrence. The following adjuvant endocrine therapy regimens are acceptable on the basis of current data: aromatase inhibitor for 5 years; tamoxifen for 2-3 years followed by an aromatase inhibitor for a total of 5 years of endocrine therapy; and tamoxifen for 5 years followed by letrozole for 2-3 years. Ongoing studies will determine whether even longer therapy with aromatase inhibitors is beneficial. In women at increased risk for developing breast cancer, tamoxifen has been shown to reduce the incidence of invasive and noninvasive breast cancers by 50%. Recently published data from the Study of Tamoxifen and Raloxifene show that raloxifene is equivalent to tamoxifen in preventing invasive breast cancer but does not reduce the risk of noninvasive breast cancer. New endocrine agents are in clinical development, and existing agents are being extended to new patient populations. [ABSTRACT FROM AUTHOR]

Even after decades of investigation, the role of high-dose chemotherapy (HDC) with autologous hematopoietic stem cell transplantation (AHST) in the treatment of breast cancer remains controversial. In preclinical and clinical studies of breast cancer in the 1980s and 1990s, dose escalation of alkylating agents—such as cyclophosphamide, carboplatin, cisplatin, etoposide, carmustine, and thiotepa—resulted in increased tumor response rates. However, the pace of investigation of HDC with AHST slowed substantially beginning in 1999 because of strong negative perceptions about AHST that arose after the report of medical research fraud in a study by Bezwoda and publication of negative results of randomized clinical trials at the 1999 annual meeting of the American Society of Clinical Oncology. Even though the number of AHST procedures performed for breast cancer has dropped precipitously over the past 6 years, more than 22 phase III clinical trials of HDC with AHST have been conducted and reported to date. The results are conflicting: some results are positive and others are negative. The safety and tolerability of HDC with AHST for breast cancer have improved greatly over the last decade. Improved preparative regimens and advances in supportive care have reduced toxicity, enhanced recovery, and markedly reduced morbidity and mortality. Many regimens can safely be administered on an outpatient basis. Clinical trials of novel uses of stem cell transplantation—e.g., autologous stem cell transplantation in patients who receive targeted therapy directed against bone metastases and circulating tumor cells; allogeneic transplants for enhancement of graft-versus-tumor effects; and use of mesenchymal stem cells as gene delivery systems—are currently being conducted or are being planned at M. D. Anderson Cancer Center. The field of stem cell transplantation continues to be a viable area of research aimed at developing innovative therapies for advanced breast cancer. [ABSTRACT FROM AUTHOR]

Over the past 30 years, numerous advances have contributed to improved survival for patients with breast cancer. Many of these advances involve the development and use of chemotherapy as adjuvant therapy and for the treatment of metastatic disease. In terms of patient survival, anthracyclinecontaining regimens are superior to non-anthracycline-containing regimens, and regimens containing both an anthracycline and a taxane are superior to regimens containing an anthracycline alone. Anthracyclines and taxanes are the cornerstones of the treatment paradigm employed at M. D. Anderson Cancer Center. This chapter outlines the M. D. Anderson approach to chemotherapy for breast cancer. [ABSTRACT FROM AUTHOR]

The routine pathologic evaluation of breast cancer must yield the histopathologic subtype, precise measurements of tumor size, and information regarding surgical margin status and lymph node status. Accurate determination of histopathologic or nuclear grade provides valuable additional prognostic information. Three molecular markers are routinely assessed to assist with treatment selection: estrogen and progesterone receptors are measured to determine eligibility for endocrine therapy, and HER-2 amplification is assessed to determine eligibility for trastuzumab therapy. Additional commercially available prognostic and predictive tests may be ordered if clinically indicated. Oncotype DX, a multigene assay, could help identify women with estrogen receptor-positive, lymph node-negative breast cancer who have a good prognosis with adjuvant endocrine therapy alone and therefore may receive little or no benefit from additional adjuvant chemotherapy. MammaPrint is a recently approved multigene assay that can assist in predicting the prognosis of women with stage I or II, lymph node-negative breast cancer. The most appropriate treatment decisions often require integration of prognostic and predictive information from multiple sources. Free and clinically validated online decision-making tools, the most widely used of which is available at www. adjuvantonline.com, are available to assist physicians in making personalized treatment recommendations based on the clinical, pathologic, and molecular features of the cancer. [ABSTRACT FROM AUTHOR]