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Grade 3 or higher left ventricular systolic dysfunction was also reported more frequently in the control group versus the pertuzumab group (2 causes of erectile dysfunction include quizlet buy 20 mg vivanza fast delivery. Therefore, more information on the cardiac safety of pertuzumab in trastuzumab pretreated patients will be available in the future. Strategies for Prevention of TreatmentAssociated Cardiotoxicity Dexrazoxane: Several strategies to prevent and treat anthracycline-induced heart failure have been developed. Dexrazoxane is a cardioprotective agent that may have a role in preventing anthracycline-induced cardiomyopathy in highrisk patients. There was also no difference in progression free or overall survival in patients treated with or without dexrazoxane. In this meta-analysis, no definitive conclusions could be made regarding adverse effects of dexrazoxane (90). In the 2008 American Society of Clinical oncology guidelines issued on the use of cardioprotectants, the expert panel suggested that clinicians consider use of dexrazoxane for patients with metastatic breast cancer and other malignancies in patients who have received more than 300 mg/m2 doxorubicin who may benefit from continued doxorubicin-containing therapy (91). One study of 201 consecutive patients with anthracycline-induced cardiomyopathy and left ventricular ejection fraction 45% or less evaluated treatment with enalapril and carvedilol. There were many patients who had not received anthracyclines as part of their chemotherapy regimen, so the broader applicability of this study to patients with anthracycline-induced cardiomyopathy is yet to be determined (93). Additionally, it is not known whether the use of these therapies as cardioprotective agents has any influence on breast cancer outcomes. Exercise to Prevent Cardiotoxicity Aerobic exercise forms an integral part of the cardiac rehabilitation programs used to treat patients with heart failure. Therefore, the use of exercise therapy for patients treated with doxorubicin has been evaluated. However, studies in humans are necessary to assess whether these findings from animal studies are relevant to humans and, if so, whether exercise affects both acute and chronic cardiomyopathy. For contralateral breast cancer, there was an estimated excess absolute risk of 2 cases per 10,000 person-years and for solid tumors 4 cases per 10,000 person-years. Of the solid tumors, most were located in areas receiving a higher dose of radiation such as the lung and esophagus (96). These findings were substantiated in a second retrospective analysis of 647,672 patients across 15 primary solid cancer types who were analyzed for the development of a second cancer. Patients who were treated with and without radiation therapy were included in the analysis. Patients were excluded from the analysis if they did not survive to 5 years, given the latency period of secondary cancers. Among all patients, 60,271 (9%) developed a second solid cancer, of which 3,266 were estimated to be related to radiotherapy, corresponding to a risk of five excess cancers per 1,000 patients treated with radiotherapy by 15 years after diagnosis. In the specific subset of patients with breast cancer, there was a 5% increased risk in secondary cancer attributable to radiotherapy. The risk decreased with later year of treatment, suggesting that newer radiation techniques may be safer (97). These two analyses, while confirming that there is an increased risk of secondary cancer in breast cancer patients receiving radiation, also confirm that the absolute risk is low. In the breast cancer population, 10% of patients developed a second cancer of which only 0. This indicates that other factors, both patient and treatment related, are involved. Summary the cardiac effects of breast cancer therapy have a major impact on quality of life and longevity of a subgroup of patients. Over the past several years we have identified patients at greatest risk of cardiotoxicity, based on baseline cardiac function. However, in the future the identification of genetic characteristics and biomarkers that indicate increased susceptibility to treatment-related cardiotoxicity will play a greater role in risk stratification of the individual patient. Currently, we are developing therapies that maintain efficacy while reducing risk of cardiac dysfunction. To date, a single susceptibility locus, in which allelic variants display a high-penetrance for radiogenic cancer, has not yet been identified. More likely, the development of a radiogenic cancer results from the coinheritance of multiple polymorphisms that increase risk in an additive fashion. Similar genetic factors that render a patient more susceptible to developing breast cancer in the first place may also contribute to developing a radiogenic cancer. Women with a second, asynchronous, contralateral breast cancer (cases) were compared with women with unilateral breast cancer (controls) matched by radiation treatment. Those women under the age of 40, who received higher doses of radiation, had an elevated risk of developing a second primary breast cancer (98). Now, with improved survival, the development of a second nonbreast malignancy, as a result of treatment, remains a major concern. While secondary malignancies are uncommon, they can be life threatening in an otherwise "cured" breast cancer survivor. In addition, there are concerns raised regarding the development of contralateral breast cancers. These leukemias are distinguished by certain morphologic and cytogenetic features. Radiation and chemotherapy together confer a greater risk of second cancers than either alone. A threefold increase in risk was observed among patients treated with radiation alone and a sixfold increase in risk among patients treated with radiation and chemotherapy indicating a possible synergistic effect of radiation and chemotherapy. Tamoxifen, a selective estrogen receptor modulator, has been used for adjuvant treatment since the 1970s and remains the first-line adjuvant endocrine therapy in premenopausal women. Tamoxifen has also been shown to effectively prevent breast cancer in women at higher risk. It has agonist activity in several tissues of the body, including the endometrium.

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Anthracyclines Since their introduction in the 1980s erectile dysfunction treatment ginseng generic vivanza 20 mg without prescription, anthracyclines have remained one of the most active agents for breast cancer. The risk of congestive heart failure is dose-related and rises from about 5% at a cumulative doxorubicin dose of 400 mg/m2 to 16% at cumulative doses of more than 500 mg/m2 (50). The use of anthracyclines in the metastatic setting is limited by acute toxicities such as nausea, vomiting, myelotoxicity, alopecia, and long-term issues such as leukemogenic risks and cardiotoxicity. There was a trend towards a worse clinical outcome (response rates and survival) for those with prior adjuvant chemotherapy, and this was statistically significant in two studies (58,59). Hence, the use if anthracyclines as first-line treatment for those already exposed to adjuvant anthracyclines is generally not recommended. In a study conducted on behalf of the Spanish Breast Cancer Research Group, patients who did not have progression after three cycles of doxorubicin 75 mg/m2 followed by three cycles of docetaxel 100 mg/m2 administered 3-weekly were then randomized to liposomal doxorubicin 40 mg/m2 once every 28 days for six cycles or observation (38). Liposomal doxorubicin was well tolerated with only 5% experiencing grade 3 or 4 fatigue, mucositis or palmar-plantar erythrodysesthesia. Hematologic toxicities were slightly greater with 12% experiencing neutropenia but only two with febrile neutropenia. However, non-crossresistance between conventional and liposomal doxorubicin and the appropriateness of treating patients who have progressed on conventional doxorubicin with liposomal doxorubicin cannot be assessed from this study. Moreover, there was less cardiotoxicity for the liposomal doxorubicin formulation. Hence, patients who were exposed to adjuvant anthracyclines may remain responsive to liposomal formulations of anthracyclines. However, epirubicin was associated with less nausea, vomiting, neutropenia, and cardiotoxicity. Taxanes Until the development of taxanes in the 1990s, treatment options were much more limited. The conclusion was that taxanecontaining regimens were more effective than some, but not all nontaxane regimens. Taxanes have been studied in two main groups of patients; those who are anthracycline-naive and those who have been anthracycline pretreated. No significant differences in response rates or median survival were observed at equal doses of epirubicin and doxorubicin. Febrile neutropenia was more prevalent in the doxorubicin group, including cardiotoxicity, nausea, vomiting and stomatitis, whereas there was more diarrhea, neuropathy, fluid retention, skin and nail changes with docetaxel. At crossover to doxorubicin or paclitaxel during second-line therapy, response rates were 30% and 16%, respectively. The doxorubicin arm was more toxic than paclitaxel in terms of hematologic, gastrointestinal, and cardiac side effects, but counterbalanced by better symptom control. However, the dose of paclitaxel used in practice is usually 175 mg/m2 as higher doses have greater toxicities but have not demonstrated a better efficacy (70). Paclitaxel monotherapy is also active in those who have been exposed to anthracyclines. Paclitaxel 175 mg/m2 every 3 weeks was found to be inferior to 3-weekly cisplatin/oral etoposide in patients with advanced breast cancer pretreated with anthracyclines (73). Inference from the available data suggests that docetaxel may be superior to 3-weekly paclitaxel. However, docetaxel maintenance therapy is often limited by hematologic toxicities, peripheral neuropathy, fatigue, nail changes, and fluid retention. Notably, docetaxel has not been compared to the more commonly used weekly paclitaxel schedule, which has demonstrated a survival advantage over the 3-weekly regimen. Owing to a 30% incidence of grade 3 sensory neuropathy, the starting dose of weekly paclitaxel was amended from 100 mg/m2 to 80 mg/m2. Anthracycline Pretreated Patients Although grade 3 or more neutropenia was more frequent with the 3-weekly compared to weekly regimen (15% vs. Grade 3 neuropathy was a treatment-limiting toxicity more common with the weekly regimen (24% vs. On the contrary, nail changes and epiphora were significantly lower in the 3-weekly docetaxel schedule. Most hematologic and nonhematologic toxicities were related to increasing doses, including those of febrile neutropenia rates (4. Hence, lower doses of docetaxel must be considered for those who are more frail or who have tolerability issues. There is evidence of an incomplete cross-resistance between paclitaxel and docetaxel, since modest responses are still seen in those exposed to the alternate taxane (80,81). However, using a taxane after progression on the other may be best reserved for patients who relapse more than 12 months after adjuvant taxane-containing therapy or who had previous clinical response to taxanes with a reasonable time lapse of at least a year. The data suggest that treatment with an alternative taxane can result in objective responses. Studies support the notion that there is only partial cross-resistance between paclitaxel and docetaxel. However, it should be noted that there was wide variation in extent of prior anthracycline and/or taxane exposure in these studies, as well as the dose and schedule of taxanes used. Nab-paclitaxel is a Cremophor-free, albumin-bound formulation designed to distribute into tumor tissue more rapidly and at higher concentrations than conventional paclitaxel, thus possibly improving drug delivery and reducing toxicity.

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Patients may present with a palpable mass or a mammographically detected lesion diabetic erectile dysfunction pump cheap 20 mg vivanza with amex, similar to carcinomas of no special type. These sizes are significantly larger than invasive carcinomas of no special type (73). Histopathology these tumors are characterized by clusters of cells in a micropapillary or tubular-alveolar arrangement that appear to be suspended in a clear space. Furthermore, four or more lymph nodes were involved in 82% of cases, and on average, nine lymph nodes were positive for metastatic carcinoma. Follow-up information was available for 12 patients, and of these, 6 died an average of 22 months after their initial treatment (73). In a different study of 80 cases of invasive micropapillary carcinoma, 47 (72%) of 65 cases with axillary lymph node dissections had positive lymph nodes (74). Another study that analyzed both pure and mixed invasive micropapillary carcinoma found axillary lymph node metastases present in 77% of cases. The metastases were typically multiple, with 51% of cases having 3 or more positive nodes (75). Interestingly, the clinical outcome of tumors with invasive micropapillary histology did not differ from infiltrating ductal carcinomas of similar stage and nodal status (75). These findings suggest that while carcinomas with an invasive micropapillary component typically present with higher-stage disease than patients with invasive carcinoma of no special type, when adjusted for stage, the prognosis of these two groups is similar. Clusters of neoplastic cells, some forming glands, are present in clear spaces separated by fibrovascular tissue. The overall appearance of invasive micropapillary carcinoma may mimic serous papillary carcinomas of the ovary, or may simulate lymphatic/vascular space invasion (72). Cytologically, the cells comprising the invasive micropapillary carcinoma usually have low to intermediate grade nuclei. An invasive micropapillary component is found in approximately 6% of all breast carcinomas (75). However, this component usually makes up a small proportion of the overall tumor, involving less than 20% of the tumor mass in one study (75). In most reported cases, invasive micropapillary carcinomas have been admixed to a variable degree with invasive carcinomas of no special type or, in a minority of cases, with mucinous carcinoma. However, unlike other special type carcinomas, the prognostic implications appear to be the same whether the micropapillary component is present focally or diffusely within the tumor (73,75). There are numerous published reports describing various aspects of metaplastic carcinomas, and numerous appellations have been applied to the various tumors comprising this group. However, there is no uniformly agreed-upon classification scheme for these tumors. Metaplastic carcinomas are uncommon lesions, representing less than 5% of all breast cancers. The prognostic implications of metaplastic carcinomas are difficult to define, and may relate to some degree to the type of metaplasia present, as discussed below. Biomarkers the majority of invasive micropapillary carcinomas are estrogen receptor positive (72% to 75%), and about half are positive for progesterone receptor. Of interest, similar alterations have been found in both the micropapillary and nonmicropapillary areas in mixed micropapillary carcinomas (78,79). In gene expression profiling studies, invasive micropapillary carcinomas are usually classified as luminal A or luminal B subtype (24). Clinical Presentation Patients with metaplastic carcinoma are similar to patients with invasive carcinoma of no special type with regard to their age at presentation, the manner in which their tumors are detected, and the location within the breast in which these tumors arise (81,82). Most patients present with a single palpable lesion that not infrequently is associated with rapid growth of short duration (82). Skin fixation has been noted in 35% of patients and fixation to deep tissues in 23% of patients in one study (81). Most are fairly circumscribed, noncalcified lesions, which in many cases appear benign (83). Some show both a circumscribed portion and a spiculated portion, which in one study correlated with the metaplastic and invasive epithelial components, respectively (83,84). Cystic degenerative changes are not infrequent, particularly in lesions with squamous differentiation. In general, metaplastic carcinomas tend to be relatively large tumors, compared to invasive carcinomas of no special type. Histopathology Microscopically, metaplastic carcinomas are highly distinctive, but vary in the types and extent of metaplastic changes. Metaplastic carcinoma with mesenchymal differentiation most commonly shows chondroid and osseous heterologous elements. In these tumors, the cartilage and bone may appear histologically benign or frankly malignant, resembling chondrosarcoma and osteosarcoma, respectively. If the heterologous metaplastic component of a particular tumor predominates, the differential diagnosis will include a malignant phyllodes tumor with heterologous elements and stromal overgrowth, as well as a pure sarcoma, either primary or metastatic. The correct diagnosis in such cases may require extensive tissue sampling in order to demonstrate epithelial elements. In some cases, immunohistochemical staining for epithelial markers, such as cytokeratin, may be required for proper diagnosis. A panel of cytokeratin antibodies may be necessary, including broad-spectrum and high-molecular weight/basal cytokeratin antibodies, as keratin immunoreactivity may be only focal.

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These procedures are most useful in smallbreasted women to match a contralateral implant reconstruction and can be performed either with or without a simultaneous mastopexy erectile dysfunction caused by statins 20 mg vivanza buy with visa. Augmentation of the nonreconstructed breast can also be performed to match a larger autologous tissue reconstruction. In some cases, augmentation is performed to augment an autogenous tissue reconstruction. This scenario is encountered in cases where the amount of autogenous tissues available. Implants used for augmentation are most commonly placed under the pectoralis muscle; however, the implant is not completely covered by the pectoralis. Instead, similar to cosmetic augmentation procedures, implants used for augmentation of the native breast in cancer survivors are covered by only the muscle superiorly. The inferior portion of the pectoralis flap is dis-inserted such that the lower portion of the implant is in a submammary position. Subpectoral implant placement is thought to decrease the rate of capsular contracture, diminish visible rippling of the implant, and facilitate mammographic surveillance of the breast. The most common surgical complication of breast reduction or mastopexy is minor wound healing complications. These occur most commonly at the "T-point" where the vertical and horizontal incisions come together. Fortunately, most of these complications are minor and heal spontaneously with conservative management. Hypertrophic scars or keloids can also be troublesome particularly in African American or Asian patients. These complications can, on occasion, be treated with steroid injections, laser, or reexcision. Reexcision combined with low-dose radiation therapy delivered directly to the scar immediately after scar excision is very successful with low rates of recurrence but require coordination with radiation oncologist (50). It is estimated that 3% to 5% of women who undergo mastopexy or reduction experience loss of nipple sensation (51). On rare occasions (<1%), women complain of long-term pain after mastopexy, reduction, or augmentation. The cause of these pain syndromes is unknown but likely reflects nerve damage or scarring. Late infections (more than 3 months after surgery) are also a rare complication but can present with erythema, pain, and fevers. These complications usually respond to antibiotic treatment but on occasion require imaging, long-term antibiotic treatment, or drainage. Another rare complication in these cases is diagnosis of incidental breast cancers or high-grade lesions. Surprisingly, reports in breast cancer survivors treated with contralateral procedures have reported even lower rates most likely reflecting the fact that this patient population is more closely followed with breast imaging (52). The main problem in cases of incidental breast cancer diagnosis is positive margins. This situation creates a treatment dilemma and in some cases may require conversion to mastectomy. Reconstruction at the time of cancer resection is an option in patients with large or ptotic breasts who desire a breast reduction or lift. These procedures often use standard surgical approaches for reduction or mastopexy and can reshape the breast to minimize contour deformities, nipple malposition, or size asymmetry that may occur after partial breast resection without reconstruction. Partial mastectomy in conjunction with breast reduction may also enable the oncologic surgeon to remove large portions of the breast (larger than would be ordinarily removed during a partial mastectomy), thereby increasing the size of the margin and potentially decreasing the risk of positive margins or local recurrence. A key issue in performing these procedures at the same time as oncologic resection is margin clearance. A positive margin may be more difficult to deal with in this setting because the breast tissue has been rearranged to a certain extent and additional resection may require opening the entire breast incision. Innovative approaches to this problem such as additional margins at the time of resection, marking the borders of the resection with clips, and so called immediate-delayed procedures in which the reconstructive procedure is performed shortly after confirmation of definitive negative permanent margins may decrease the potential for these problems (53). Breast reduction or lifts are well tolerated and associated with a low rate of complications. The primary complications include minor wound healing issues, seroma, hematoma, loss of nipple sensation, and breast asymmetry. Of these complications, asymmetry is particularly problematic due to the fact that these patients are treated with unilateral radiation therapy that may cause unexpected breast tissue shrinkage or skin fibrosis. For this reason, patients are advised that follow-up procedures may be necessary in the future to correct these problems. Patients with small or nonptotic breasts may also be candidates for immediate partial breast reconstruction in an effort to avoid mastectomy or significant contour deformities that may result from partial mastectomy. In these cases, local tissue flaps from the back, or more rarely, from the abdomen, are transferred to the breast at the time of tumor resection to replace breast tissue or skin and restore the normal contours of the breast. This approach is somewhat controversial since some reconstructive surgeons argue that a potential option for reconstruction is lost in case the patient has a recurrence and requires a mastectomy. Those in favor of these procedures note that breast recurrence in these patients is relatively infrequent particularly if postoperative radiation is performed and that other options or donor sites are frequently available even if there is a recurrence. Plastic surgeons are also frequently consulted for reconstruction of partial mastectomy defects in patients who had previously undergone breast resection and radiation. These patients usually present with breast asymmetry due to resection or radiation-induced fibrosis, contour deformities, or nipple malposition. Asymmetry in these cases is often due to a combination of breast volume deficit and skin fibrosis causing decreased relative ptosis of the radiated breast. Although reconstruction in this setting is more difficult due to increased scarring and history of radiation, a number of techniques are available ranging from relatively simple to more complicated.

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Implant reconstructions are safe and well tolerated with low rates of major and minor complications (5) impotence yahoo answers order vivanza 20 mg free shipping. There were no cases of life-threatening complications (pulmonary embolus, myocardial infarction, major systemic complication) in a recent review of over 1,170 consecutive reconstructions performed at Memorial Sloan-Kettering Cancer Center (5). The majority of complications that did occur were minor and included skin necrosis (8. Capsular contracture is the most significant long-term risk with implant reconstructions and remains a problem even with improvements in implant technology and surgical techniques (7). The reported rates of capsular contracture vary significantly likely due to the fact that the diagnosis of this complication is somewhat arbitrary and not uniform. Most studies use the Baker scale as noted above; however, this scale has been criticized since it is not quantitative and primarily dependent on subjective assessment of "normal" or "abnormal" breast shape. This subjective assessment is likely responsible for the significant variability in the reported rates of capsular contracture and overall success rates of implant reconstructions in the plastic surgery literature. Another important issue in comparing aesthetic outcomes in implant reconstruction is the methods used for analysis. By far the vast majority of previous studies have relied on photographic analysis by surgeons or laypeople to analyze various measures including symmetry, scars, volume, shape, and so on. Although these results are important and provide useful information, they do not address patient perceptions and may either over- or underestimate the success rates of various reconstructive needs. The addition of these measures is exciting and provides surgeons with better insight about how patients perceive their reconstruction. This information can therefore help guide reconstructive techniques, preoperative teaching and preparation, and critical analysis of outcomes that can be standardized across centers. In the past, a major concern limiting access of patients to immediate reconstruction was a hypothetical increase in the risk of breast cancer or delay of diagnosis of a recurrence in this setting. However, several large-scale studies have shown that immediate reconstruction with implants has little effect on recurrence, survival, or diagnosis of recurrence (5). The majority of recurrences in these cases were skin or subcutaneous in nature and identified by routine physical exam or serological markers. For this reason, follow-up of patients with implant reconstruction is usually limited to careful physical exams rather than mammography or other radiological measures. Even when patients were discovered to have a recurrence, implant reconstruction in the majority of cases did not alter additional treatment (5). A number of risk factors predict complications after implant based breast reconstruction. In a study of 1,170 consecutive reconstructions using multivariate analysis, McCarthy and colleagues demonstrated that obesity, hypertension, age greater than 65, and smoking were independent predictors of complications (2). Univariate analysis of reconstructive failure demonstrated that obesity, smoking, and hypertension significantly increased the risk of reconstructive failure. Several studies have reported satisfaction with implant reconstructions and most have reported high rates of satisfaction in the early years following reconstruction. However, a consistent theme is decreasing satisfaction over time that may be attributable to a number of factors including lack of change in the implant over time, the need for implant maintenance (either for symmetry or due to rupture), and capsular contracture. Many of the reported studies have used nonvalidated questionnaires, thereby making their findings somewhat less useful. In most patients the latissimus flap does not have enough volume for a full breast reconstruction, and for this reason, it is usually combined with an immediate implant or expander placement. The latissimus flap can be used in primary breast reconstruction after mastectomy or as a salvage procedure for patients who have failed other forms of breast reconstruction. Although most surgeons use the latissimus flap for unilateral reconstructions, bilateral reconstructions have also been reported. The latissimus flap is an excellent option in morbidly obese patients with massive breasts (14) and in smokers, although the risk of minor wound healing complications in this population remains elevated as compared with normal weight women and nonsmokers, respectively. The main contraindication to the latissimus flap is a previous thoracotomy operation that transects the latissimus muscle/pedicle, or a history of pedicle ligation. The blood supply or pedicle for the latissimus dorsi flap is the thoracodorsal vessels, which may on occasion be injured during the course of axillary lymph node biopsy or dissection. Testing the ability of the patient to flex the latissimus dorsi muscles is a simple way to test the integrity of the pedicle vessels since the thoracodorsal nerve, artery, and vein are intimately associated. Therefore, if the thoracodorsal nerve function is preserved it is likely that the vessels are likewise preserved. A variety of skin paddle designs have been reported for the latissimus transferring a variable amount of skin and soft tissues to the breast. In some cases, no skin is necessary in which case the muscle can be harvested through several short incisions to decrease the donor site scarring. The oblique flap design has a more noticeable donor site scar but is more useful if a larger skin paddle, such as may be needed in a delayed reconstruction, is necessary. The Fleur-de-lis modification combines both vertical and horizontal components and enables transfer of a large amount of tissues in many cases obviating the need for an implant (15). However, this flap design results in a T-shaped scar with a confluence of three incisions at the point of maximal tension and can be, as a result, associated with increased rates of donor site wound healing complications and contour deformity. In most cases an implant is also necessary to obtain the necessary volume and projection of the contralateral breast. However, most commonly, a tissue expander is placed in order to adjust for latissimus muscle atrophy and to more slowly expand the breast pocket.

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Although racial disparities in breast cancer treatment are generally well-documented can you get erectile dysfunction age 17 purchase vivanza with amex, more racially specific data are needed in some areas. Additionally, racial differences may exist in receipt of post-mastectomy radiation therapy (indicated at a minimum for tumors greater than 5 cm or with multiple positive nodes). Punglia and colleagues examined receipt of radiation therapy after mastectomy in elderly women during the 1990s and found that trends in use differed significantly across practice settings, but more updated examinations by race are needed (75). Differences in treatment can potentially explain a large portion of the racial and ethnic disparities in breast cancer, particularly among patients eligible for radiation and endocrine therapies. In many cases, however, racial differences in mortality remain even after controlling for treatments received, and racial differences persist in health systems with equal insurance coverage and access to care (23). These realities suggest a need to explore other factors that may contribute to poorer outcomes among minority breast cancer patients, including differences in treatment response and survivorship care. A single institution cohort study found lower baseline and posttreatment white blood cell counts among black women, and these lower counts were associated with reduced chemotherapy dose intensity due to dose reductions. Rates of serious chemotherapy-associated side effects including neutropenic fever and toxicity requiring a treatment delay did not appear to differ by race within a clinical trial population (77), though treatment delays for any reason were significantly more common in black women. The effect of toxicity-mediated disparities in treatment intensity on recurrence and survival outcomes is not yet understood. Black women may also experience a disproportionate side effect burden from treatments other than chemotherapy. Black race has been reported as an independent risk factor for the development of lymphedema, or swelling of the arm after breast cancer surgery (78). Additionally, black and Hispanic women are more likely than white women to experience inadequate pain management and management of serious side effects of treatment (79). Differences in efficacy On the whole, evidence suggests that black and white women receiving similar breast cancer treatment experience similar outcomes. Patients treated with neoadjuvant chemotherapy (chemotherapy given before definitive breast cancer surgery) have been a logical population in which to study this question, because pathologic findings at surgery provide a quantifiable patient-specific measure of response to chemotherapy. This analysis was not able to control for receipt of, or adherence to , endocrine therapy. No significant difference in outcome was seen in patients with hormone receptor negative tumors, again raising the question of whether access or adherence to long-term endocrine therapy may influence disparities among women with hormone receptor-positive tumors. Similar patterns of response have been observed in patients receiving adjuvant rather than neoadjuvant chemotherapy. Both possibilities have been explored most thoroughly in the area of chemotherapy treatment. Concerns have been raised for greater hematologic toxicity of chemotherapy among black patients due to lower baseline white blood cell counts (51). No interaction between race and receptor subtype was found in this study, suggesting a consistent effect across breast cancer subtypes, but the strength of this finding is limited by a relatively small sample size. In summary, the evidence suggests that response to chemotherapy in women with similar disease characteristics is comparable across races, and that observed differences in long-term breast cancer recurrence and survival outcomes after chemotherapy are most prominent in hormone receptor-positive subtypes, where outcomes may be affected by differences in use of endocrine therapy. It is also possible that within-subtype biologic differences explain worse outcomes among black women with hormone receptor-positive tumors, suggesting a need for more research focused on molecular characterization of these tumors. Older studies suggested that black survivors might have more difficulty with resumption of daily tasks and long-term adjustment compared to whites (83), but research to substantiate or add detail to these findings is lacking. There is some evidence that minority women receive less adequate supportive care during the survivorship period. In one survey study, black and Hispanic women were less likely than whites to report talking with other survivors, and more likely to report wanting more contact with other breast cancer patients (84). Black and Hispanic breast cancer survivors in another survey of survivorship care were more likely to report an unmet survivorship-related need, such as menopausal symptoms, difficulty sleeping, or arm problems. Both cost/insurance and barriers and problems in communicating about needs with providers were cited by women as reasons for unmet needs (85). Overall health utilization among black women after breast cancer may also lag that of white women. In a large cohort study, black breast cancer survivors were less likely than their white counterparts to receive preventive healthcare services, such as influenza vaccination, lipid screening, and screening for other cancers, after adjustment for age, comorbidity and a variety of disease-related and socioeconomic factors (86). Although there is little research regarding the underlying causes of these disparities in survivorship care, it is reasonable to hypothesize that patient-, provider-, and structural-level factors affecting receipt of high quality care during initial treatment may have similar effects during survivorship. Interactions among these patient-level factors may have an additive or multiplicative negative effect on health outcomes. For example, the issue of distance to care has been found to be more problematic for older women (88) and Hispanic women (37), perhaps suggesting that transportation to care is particularly problematic in these subgroups. High quality data as well as complex analytic methods are required to correctly understand interrelationships among multiple patient-level factors affecting the quality of breast cancer care. It should be noted that the relationship between race and other factors that affect breast cancer risk and cancer care utilization is complex and that the needs or challenges of breast cancer patients of a given race may differ based on factors linked to , but distinct from, race. To cite one example, multiple studies have documented that use of adjuvant endocrine therapy is uniformly lower among Medicaid patients, who typically have low income and poor healthcare access, than has been reported in other patient populations, and this underuse is uniform across Medicaid patients of different races despite the over-representation of black women in Medicaid (58,60). In this case, socioeconomic vulnerability, not race, is likely the driver of underutilization and attenuates racial differences. Conversely, within-group heterogeneity in racial minorities is often understudied such that the variations in utilization within minority populations are masked. For instance, although Asian women in Northern California have been reported to initiate adjuvant endocrine therapy at similar rates compared to whites, further sub-group analysis identified that Chinese woman actually initiate endocrine therapy at lower than average rates, while other Asian subgroups including Japanese, Filipino and South Asian women initiate at average rates (59). Within-group heterogeneity in breast cancer also occurs within immigrant populations; U. These complex relationships illustrate that disparities in breast cancer among minority women are indeed multifactorial and likely will require equally complex solutions. Organizational, structural, economic, and sociopolitical dynamics of the American health system contribute to complex racial/ethnic, socioeconomic, age-related, and geographic health disparities.


  • Difficulty breathing (the infant needs to work hard to breathe)
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Pathological complete remission rates were 31% erectile dysfunction injection medication order genuine vivanza on-line, 23%, 49%, and 18%, for the four arms, respectively, indicating that combining the two antibodies with chemotherapy provides the best result, while the two antibodies without chemotherapy were able to eradicate the primary tumor in almost 20% of patients. Table 58-2 lists the more commonly used effective and well-tolerated neoadjuvant chemotherapy regimens. More limited information is available about neoadjuvant endocrine therapy (see also Chapter 55, Preoperative Endocrine Therapy for Operable Breast Cancer). The initial trials used tamoxifen and included patients selected on the basis of old age or comorbidity that precluded chemotherapy (49,50). A significant minority of tumors progressed during neoadjuvant endocrine therapy; thus, close monitoring is required so that early progressors are identified promptly and appropriate regional therapy (or crossover to chemotherapy) can be implemented. Several studies also concluded that tamoxifen alone was insufficient therapy for patients with primary and locally advanced breast cancer, and that appropriate surgery and/or radiation therapy was needed for optimal local and systemic control (51,52). More recent trials compared selective aromatase inhibitors with drugs in the same family or with tamoxifen (53). Greater antitumor efficacy was observed with aromatase inhibitors compared to tamoxifen (53). Early progression is observed more frequently after neoadjuvant endocrine therapy (12% to 17%) (53) than after neoadjuvant chemotherapy (5% to 10%) (6). Because malignant lesions are typically more vascular than benign lesions, they tend to take up the contrast agent faster. They can also be distinguished from benign lesions by having spiculated rather than smooth edges. However, the false negative rate associated with physical examination has been reported to be almost 60% (54), indicating that many small tumors might be missed using this approach. This problem can be resolved by running the scan concurrently or sequentially with an alternate anatomical imaging modality. Surgical therapy may require a total mastectomy or only breast-conserving surgery (also referred to as wide excision, lumpectomy, or quadrantectomy), both with an axillary surgery (see also Chapters 33, Mastectomy; 35, Breast-Conserving Therapy, and 38, Axillary Dissection). As with any curative breast cancer surgery, the primary goal is to completely remove the tumor with negative margins. In addition, nearly two-thirds of the patients with a clinical complete response will prove to have residual tumor on final pathology, so it is critically important to be able to precisely localize and remove the original tumor site and ensure that the surgical specimen has clean margins (65). Placement of two or more markers should be considered for multifocal disease in patients who are interested in breast conservation. Mammography is performed immediately after marker implantation to precisely document the position of the marker in relation to the tumor. Bracketing with two or more guidewires is used for patients with extensive calcifications or multifocal disease at the onset. Surgical excision does not attempt to remove the pre-chemotherapy volume of tumor. Rather, the goal is to remove any residual lesion with 1 cm of clear margins or, if there is no detectable residual lesion, a 2-cm specimen with the metal coil in the center. Margins are inked; a multicolor inking system may be used to identify the superior, inferior, lateral, medial, anterior, and posterior surfaces. While the patient is still in surgery, the specimen may be sectioned, with the order of all sections maintained so that the site of any positive or close margin can be identified and the surgeon can remove additional tissue from this area to obtain a negative margin. Classification of a tumor as T4b indicates the presence of noninflammatory skin changes, including edema, ulceration of the skin of the breast, or presence of satellite skin nodules confined to the same breast. However, emerging data suggests that carefully selected patients with noninflammatory T4b disease may be candidates for breast conservation. Shen and colleagues (66) looked at local control and long-term survival in 33 patients with noninflammatory T4b disease treated with breast conservation therapy. The 5-year overall survival rate was 78%, superior to most published survival data for patients with noninflammatory T4b disease, likely reflecting the careful selection criteria that were used. This is true even for selected patients with skin ulceration, among the most alarming of symptoms and one that is usually associated with longneglected locally advanced disease. For example, tumors of the inframammary fold can be quite small (1 cm) and present with skin ulceration. These patients can be treated conservatively with en bloc excision of the involved skin if the tumor demonstrates direct tumor invasion/ulceration, with favorable outcomes. Current reconstructive techniques using autologous tissue flaps offer excellent cosmetic results without compromising long-term outcomes (see Chapter 36). Ideally, breast reconstruction can be carried out during the same surgery as the mastectomy, lessening the cost and the risk of multiple surgeries. Immediate breast reconstruction can be an important factor in recovery, contributing to a more positive body image. Mean followup times for the immediate reconstruction and delayed reconstruction groups were 3 and 5 years, respectively. Late complications, including fat necrosis, volume loss in the flap, and contracture in the flap, were significantly more common in patients with immediate reconstruction. Fat necrosis occurred in 44% of patients with immediate reconstruction compared with 9% of patients with delayed reconstruction. No patients with delayed reconstruction experienced volume loss or contracture, versus 88% and 75%, respectively, of patients receiving immediate reconstruction.

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C Reexcision Following Narrow Margin excision Approximately 20% of phyllodes tumors recur locally if excised with inadequate margins erectile dysfunction medication muse discount vivanza on line. The proportion of recurrences appears to be somewhat higher with borderline or malignant varieties and lower with benign phyllodes tumors (52), with most authors demonstrating a benefit to negative margin resection for all histologic types secondary to all lesions having a propensity to recur with anything short of wide local excision (Table 62-2). Technical Considerations in lumpectomy In order to achieve 1 cm or greater surgical margins with lumpectomy, special approaches may be necessary, particularly when a phyllodes tumor develops in a smaller breast. Tunneling through the fibroglandular tissue from a periareolar incision is contraindicated with phyllodes tumor excisions because of the potential for tumor seeding. Full thickness excisions from skin to chest wall muscle can be very helpful in achieving the 1 cm desired surgical margins. This approach allows en bloc removal of skin, tumor, and surrounding fibroglandular tissue in an oncoplastic fashion. The excision is then carried out full thickness from the skin island, widely around the mass, and down to and including the pectoral muscle fascia. Anderson experience of 101 patients with phyllodes tumors (2), surgery included local excision with breast conservation (47%) or mastectomy (53%). The investigators concluded that local failure was uncommon, showing that breast-conserving surgery with negative margins is the preferred primary therapy. Kleer and colleagues found that malignant phyllodes tumors have a favorable prognosis if widely excised without mastectomy (18). Multiple additional series have also failed to show a benefit to mastectomy over lumpectomy in patients who are otherwise good breast conserving therapy candidates, regardless of tumor histology, provided negative surgical margins can be achieved with lumpectomy (34). Adjuvant radiation therapy may be considered appropriate treatment for selected locally recurrent phyllodes tumors, such as following mastectomy. Unfortunately, recurrent phyllodes tumors arise so infrequently and the biologic profiles of recurrent phyllodes tumors are so heterogeneous that no large series of locally recurrent phyllodes tumors is ever likely to be collected. If adjuvant radiotherapy is utilized, it would be reasonable to use the guidelines for soft tissue sarcomas, which entail treating the entire breast tissue or chest wall in the radiation fields to deliver 50 to 50. After completion of the primary fields, treatment would proceed with a generous tumor bed or mastectomy scar boost with an additional 10 to 20 Gy. Combined Therapy Some reports have supported the use of combined chemoradiation following phyllodes tumor recurrence. In one case study of a locally recurrent malignant phyllodes tumor, neoadjuvant hyperfractionated radiotherapy, superficial hyperthermia, and ifosfamide were administered after the second local recurrence of this tumor. Resection of the tumor bed revealed a pathologically complete response with an actual disease free follow-up of 48 months (61). Axillary Staging Routine axillary dissection is unnecessary in patients with phyllodes tumors (26,53). In another series of 45 patients with phyllodes tumors who underwent axillary staging, none were found to have axillary metastases (55). If suspicious lymph nodes are identified clinically or on imaging studies, directed axillary ultrasound with fine needle aspiration (56) or, preferably, core needle sampling can be performed. If this work-up is negative, sentinel lymph node biopsy can be considered if there is still reason to believe that the axillary nodes are involved. In the absence of such suspicion, neither sentinel node biopsy nor axillary node dissection are considered standard care in the surgical management of the clinically node-negative patient with phyllodes tumors. Adjuvant endocrine Therapy Phyllodes tumors variably express steroid receptors, but there is no known value to adjuvant endocrine therapy with tamoxifen or aromatase inhibitors (62). There would be little rationale for using these drugs because steroid receptor protein expression decreases with increasing malignancy, they are primarily expressed by the epithelial component of phyllodes tumors, and only the stromal component of phyllodes tumors metastasizes. Overall, the systemic treatment principles of phyllodes tumors are driven by similar principles to those governing the management of soft tissue sarcoma. Systemic Therapy Chaney and colleagues observed that some patients, especially those with stromal overgrowth, particularly when the tumor size was more than 5 cm, had higher rates of distant failure. These authors suggested that such patients merit consideration of a trial that examines the efficacy of systemic therapy, even in the absence of metastatic involvement (2). Burton and colleagues found that two of three patients with metastases achieved effective palliation when treated with cisplatin and etoposide combination chemotherapy (62). Adjuvant Radiation Therapy Overall, the role of radiation therapy for phyllodes tumors remains unclear, with the majority of data derived from single-institution retrospective studies (57). For benign phyllodes tumors managed conservatively with surgery alone, adjuvant radiotherapy appears unnecessary when adequate margins are achieved. Similarly, most authors show that treatment of borderline and malignant phyllodes tumors with mastectomy alone yields excellent local control rates (2,58). Unfortunately, with lumpectomy alone, local control rates appear worse for borderline and malignant phyllodes patients (58). One study endorsed the use of adjuvant radiotherapy after breast conserving surgery for borderline or malignant phyllodes tumors larger than 3 cm, with local recurrence rates of 45% with conservative surgery alone (28), while another demonstrated the benefits of post lumpectomy radiotherapy in the treatment of malignant phyllodes tumors with a local failure rate as low as 12% (59). A 13-year institutional review found 27 women diagnosed with 19 (73%) benign, 3 (12%) borderline, and 4 (15%) malignant lesions. Of the 26 cases followed for a mean period of 37 months, 4 (16%) recurred at a mean time of 9 months following surgery, occurring among all histologic subtypes (1 benign, 1 borderline, and 2 malignant lesions) (64). The mass proved to be a malignant phyllodes tumor and was re-excised with a partial mastectomy. A subsequent mastectomy was performed using a three-sided incision to facilitate wide excision down to the level of skeletal muscle. Despite this second reexcision, the mass recurred again within 23 months, this time adjacent to the mastectomy incision. In addition to the protuberant mass, the tumor extends under the skin into the surrounding soft tissue and fat. In a Milan series of 216 patients operated on between 1970 and 1989, the average disease-free interval was 32 months for benign phyllodes tumors, 22 months for malignant, and 18 months for borderline phyllodes tumors (65). Although surgical margins remain the best predictor of local recurrence, two studies suggest that tumor necrosis is also linked to an increased local recurrence risk.

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In addition erectile dysfunction hiv medications trusted 20 mg vivanza, tumor markers may help in the diagnosis of metastatic colon or pancreatic cancers. Axillary adenopathy usually consists of one or two involved nodes, sometimes with large diameters. The median axillary node size at presentation in the patients treated at the Institut Curie was 30 mm (range, 10 to 70 mm). The initial diagnosis of malignancy was achieved by node excision in 25 of 59 patients, by fine-needle aspiration in 26 patients, and by core-needle biopsy (drill biopsy) in 8 patients. A primary breast cancer located in the axillary tail of the breast may be confounded with an axillary node. The presence of normal lymph node structure surrounding the foci of the carcinoma on the pathologic sample usually leads to the diagnosis of metastasis to a lymph node. The recognition of a metastatic lymph node can, however, be difficult because of massive involvement, with extension of the tumor into the axillary fat and disappearance of the lymphoid patterns. Breast Cancer Bilateral mammography should always be performed in the presence of metastatic adenocarcinoma in an axillary lymph node. Many of these tumors are missed owing to their relative small size and the fact that they are obscured on the mammogram by dense fibroglandular tissue (10). Mammography and ultrasound have been the primary modalities for the diagnosis and the workup of breast cancer (10). Because surgical excision of the palpable node was often the first diagnostic procedure, rarely was an attempt made to analyze the receptors by biochemical methods. In a series of 80 patients with occult breast cancer and axillary metastases, Montagna et al. However, because of its low specificity and the difficulties in localizing small, early contrast-enhancing foci in some instances, difficult management problems may occur. Invasive breast cancer was found in 9 of the 11 patients (82%) who underwent surgery. However, though it has a high specificity when detecting breast lesions, its sensitivity is low, particularly in small tumors (25). No experience has been so far reported on the use of these new techniques in the diagnosis of occult breast carcinoma. In patients who have nonpalpable breast masses and normal imaging workup, the mammary origin of a metastatic adenocarcinoma to an axillary lymph node cannot be established with certainty. Therefore, the diagnosis of occult breast cancer can only be highly presumed based on many elements, including sex, age, isolated adenopathy, and histologic diagnosis of adenocarcinoma. Natural History After removal of an axillary adenopathy, a breast cancer eventually developed in the untreated breast in an average 42% of patients, as reported in one review (2), with time intervals below 5 years in all cases. Patient samples were limited in these series, however, and follow-up periods varied widely. The number of pathologically involved lymph nodes seen after axillary dissection is high. Table 66-2 summarizes the results in five series, reporting a median number of involved nodes was close to three. Forty patients in the Institut Curie series had an axillary dissection as initial treatment. During follow-up, 16 of the 59 patients in the series had distant metastases: 4 (25%) in the brain, 5 (31%) in the liver, 3 (19%) as cervical nodes, and 3 in multiple sites. Ten patients had contralateral disease, which occurred in the contralateral breast alone in 6 patients. Treatment and Results Mastectomy with axillary node dissection has been the most commonly used treatment in patients with occult primary tumors. The combined analysis of 10 published series has shown that breast cancer was found in the mastectomy specimen in 147 of 210 patients (70%) (Table 66-3). Table 66-4 shows the results of breast irradiation in several retrospective studies. The 5-year local recurrence rates in patients who received breast irradiation ranged from 7. These data, along with the fact that nearly 50% of the patients who received no form of breast treatment will eventually have disease recurrence in the breast, support the recommendation that the breast be treated when no tumor can be detected clinically or mammographically. Whether mastectomy should be carried out in all patients, or breast conservation with whole-breast irradiation can be safely performed remains to be demonstrated. At a median follow-up of 7 years, no differences in locoregional recurrences, distant metastases, disease-free survival, or overall survival were observed between those who had a breast-conserving treatment and those who had a mastectomy. Adjuvant systemic treatment was delivered to 84% and 46% of patients, respectively. After axillary node dissection, should irradiation be delivered to the remaining lymph nodes A substantial risk for nodal involvement of the upper axilla can be suspected, however, based on the fact that three involved nodes are expected to be found in one-half of the patients. In patients with axillary node involvement associated with an invasive breast cancer, irradiation of the upper axilla is typically delivered when four or more nodes are involved. Studies have shown that, in patients with axillary node involvement, postmastectomy irradiation of the chest wall and regional nodes (39), as well as breast and nodes irradiation after breast-conserving surgery (40) decreased the rate of long-term distant metastases and improved survival, even in patients who received adjuvant chemotherapy or hormone therapy. In most instances, only the upper axilla and supraclavicular nodes were treated after complete axillary nodal dissection, whereas the whole axilla was treated when a simple adenectomy had been performed. There were four axillary node recurrences: One was isolated, but three were associated with a breast recurrence. The indications for internal mammary node irradiation are currently much debated in patients with a breast mass and central or medial tumor or axillary involvement. Because the location of the primary tumor is unknown, the Institut Curie policy supports the irradiation of the internal mammary nodes in all patients. The reported 5-year actuarial survival rates after treatment of occult breast cancer with axillary metastases range from 36% to 79% (Table 66-5). The 5- and 10-year survival estimates in the 59 patients treated at the Institut Curie were 84.

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All the studies focused on a relatively high-risk population (node positive or high-risk node negative) and all except FinHer included at least one year of trastuzumab erectile dysfunction video purchase vivanza overnight. Trastuzumab was administered concurrently with paclitaxel and was continued for a total of one year. In N9831, a third arm was included in which the year of trastuzumab was delayed until the completion of all chemotherapy. Because of the similarities of the trial designs, the investigators performed a pooled analysis of the two trials, combining the two control arms and the two investigational arms that involved concurrent administration of trastuzumab and paclitaxel. Patients from N9831 who received sequential paclitaxel followed by trastuzumab were excluded from this analysis. A total of 3,351 patients (1,679 in combined control group and 1,672 in combined trastuzumab group) were included. Both studies initially excluded node negative patients, but ultimately the N9831 trial was amended to include highrisk node negative patients (defined as a tumor >2 cm for hormone receptor positive cancers and tumor >1 cm for hormone receptor negative cancers), but less than 6% of the patients in the combined analysis had node negative disease. The addition of trastuzumab was also associated with a 33% reduction in the risk of death (p =. More recently, the final results from the pooled analysis of N9831/B31 were presented with 8. Because of the clear benefit of trastuzumab observed in the first pooled analysis in 2005, patients on the control arm of the study were offered treatment with one year of trastuzumab. These patients are included in this final analysis according to intention to treat, and if anything, this crossover would lead to an underestimation of the true benefit of trastuzumab. The eligibility criteria were relatively broad, allowing both node positive and node negative patients as long as tumor size was at least 1 cm. Ninety-four percent received an anthracycline-based regimen and 26% also received a taxane. The trastuzumab, which was given every 3 weeks, was mandated to begin no more than 7 weeks from day 1 of the conclusion of chemotherapy or 6 weeks from the completion of radiation or definitive surgery, whichever was last. This first interim analysis crossed the prespecified early stopping boundary with a median follow-up of only 1 year. As was the case with the North American trials, patients on the observation group were offered 1 year of trastuzumab; fully 52% crossed over, which presumably had an effect on the observed benefit of trastuzumab. This global study was unique in that it included an arm with a non-anthracycline regimen. For both of the trastuzumab arms, the trastuzumab was given weekly during the chemotherapy and then every 3 weeks to complete 1 year. A total of 3,222 patients were enrolled, of whom approximately 29% were node negative. The study had only limited power to detect large differences in outcome between the two trastuzumabcontaining arms. Two smaller randomized trials have also evaluated the adjuvant use of trastuzumab. A second randomization was to either observation or a year of trastuzumab (given every 3 weeks) starting after completion of the chemotherapy. The trastuzumab was started concurrent with the taxane and continued throughout the chemotherapy (24 weeks). A cohort of 22 patients was subsequently enrolled and treated in a uniform fashion with the same chemotherapy and trastuzumab regimen. After a median follow-up of 36 months, the 3-year disease-free survival for those patients randomized to chemotherapy alone was 85. Cyclophosphamide (600 mg/m2), methotrexate (40 mg/m2), and fluorouracil (600 mg/m2) were then given on days 1 and 8 every 4 weeks for three cycles. Those patients randomized to the trastuzumab arm received the antibody every 3 weeks concurrent with the entire chemotherapy regimen. They also received trastuzumab postoperatively to complete a total of 1 year of trastuzumab therapy. In the randomized studies, rates of adverse events were similar in patients assigned to receive trastuzumab relative to that of the control group (18,20,22). However, as previously discussed, the pivotal metastatic study demonstrated significant evidence of cardiac toxicity with trastuzumab, particularly when combined with an anthracycline. The data from these randomized studies thus provide valuable information regarding the cardiac effects of trastuzumab in patients with early-stage disease, including quantification of the absolute risk of cardiac toxicity, identification of treatment regimens that are more likely to be associated with cardiac effects, and characterization of risk factors that predict a higher likelihood of cardiac toxicity. There is no question that trastuzumab, particularly when given in conjunction with an anthracycline-based regimen, does have the potential to cause cardiac toxicity in the adjuvant setting (summarized in Table 46-3), but the absolute incidence of significant toxicity is low and the rates vary substantially across the trials. There are however, no data that clearly implicate prior receipt of a taxane as a risk factor for trastuzumab induced cardiac toxicity. However, given the similar rates of significant cardiac events in the sequential (2. Several studies have sought to identify patient characteristics that predict an increased likelihood of developing trastuzumab-induced cardiotoxicity. The vast majority of cardiac events occurred during the first year of trastuzumab therapy, and only two events occurred more than 2 years from the initiation of trastuzumab. Thus, at this time, there is no clear evidence to suggest that trastuzumab therapy is associated with delayed-onset cardiotoxicity.

Angar, 44 years: Despite this second reexcision, the mass recurred again within 23 months, this time adjacent to the mastectomy incision. However, this does not necessarily appear to be the case for palliative radiation for bony metastases. Update on the melanoma staging system: the importance of sentinel node staging and primary tumor mititic rate.

Will, 48 years: These concerns may contribute to the greater psychosocial distress seen in younger women at both diagnosis and in follow-up (21). One report describes reversible heart failure in the mother but no anhydramnios in the fetus (49). A "screening" midline sagittal scan is inadequate; multiple sagittal scans using thin slices should be performed.

Kan, 38 years: These cancers cluster with the basal-like group on gene expression profiling studies (24). Endocrine Therapy For patients with metastases that are detected while on adjuvant tamoxifen or whose cancer recurs greater than a year after stopping adjuvant aromatase inhibitors, initial endocrine treatment should be with an aromatase inhibitor. Gracilis musculocutaneous flaps have gained some favor for breast reconstruction over the last decade.

Ismael, 21 years: Because almost all women who have lumpectomies will receive adjuvant radiation, it is not known whether the additional surgery truly does lower local recurrence rate as compared to adjuvant radiation. Emerging results in the advanced, acquired endocrine-resistance disease setting provide strong support for prospective studies of novel targeted agents in the adjuvant setting in tumors with de novo endocrine resistance and are summarized in the "Future Directions" section of this chapter. Two placebo-controlled, double-blinded randomized trials found that paroxetine decreased hot flashes significantly more than did a placebo (18�20).

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