Prognosis after regional lymph node recurrence in patients with stage I-II breast carcinoma treated with breast conservation therapy

BACKGROUND: The authors evaluated the risk factors for regional lymph node recurrence and the prognosis of patients with regional nodal recurrence after breast conservation therapy for Stage I-II breast carcinoma. METHODS: Between 1977 and 1995, 1293 women with pathologic Stage I and II (T1-2, N0-1) breast carcinoma were treated with breast-conserving therapy including lumpectomy, axillary lymph node dissection, and definitive breast irradiation. A total of 39 women (3%) had any regional lymph node recurrence. The median follow-up was 8.5 years (range, 1.5-24 years). RESULTS: Among 39 patients with a regional lymph node recurrence, 10 women had regional recurrence only, 16 had simultaneous locoregional recurrence, and 13 had simultaneous regional and distant recurrence. Regional recurrence occurred in the axillary lymph nodes only (n = 21; 51%), supraclavicular lymph nodes only (n = 8; 23%), internal mammary lymph nodes only (n = 3; 8%), infraclavicular lymph nodes only (n = 3; 8%), or multiple lymph node sites (n = 4; 10%). The median time to regional lymph node recurrence was 3.1 years (range, 0.2-20.9 years). Overall survival after regional-only disease recurrence was 44%, locoregional disease recurrence was 26%, and regional with distant disease recurrence was 12%. Cause-specific survival rates at 10 years for the 3 groups were 44%, 40%, and 12%, respectively. For patients who presented with simultaneous regional and distant metastases, the median survival period was 1.1 years, compared with 5.2 years for women who developed distant disease subsequent to regional recurrence. CONCLUSIONS: Regional lymph node recurrence after breast conservation therapy may be salvaged, but is associated with a high rate of either simultaneous or subsequent distant metastatic dissemination and poor overall prognosis.     

Risk of early recurrence among postmenopausal women with estrogen receptor-positive early breast cancer treated with adjuvant tamoxifen

BACKGROUND: Adjuvant aromatase inhibitors (AIs), instead of or after tamoxifen, are effective in decreasing recurrence in postmenopausal women with estrogen receptor (ER)-positive breast cancer. An understanding of which patients are at risk of early recurrence while they are receiving tamoxifen may improve clinical decision making. METHODS: The patients who were included in this study were women aged >or= 50 years with early-stage, ER-positive breast cancer diagnosed between 1986 and 1999 and had been treated with tamoxifen. Characteristics of the patients with early recurrences (within 2.5 years of diagnosis), late recurrences (between 2.5 years and 5 years) and no recurrence within 5 years were compared. Logistic regression analyses were conducted to identify which groups were at risk of early recurrence. RESULTS: Among 3844 women, 304 women (7.9%) developed disease recurrence within 2.5 years. Higher than average rates of recurrence within 2.5 years were observed in cohorts with lymph node (N)-positive tumors (11.5%), grade 3 histology (14.3%), or low-positive ER levels, ie, 10-49 fmol/mg or 10%-20% staining (14.9%). In multivariate analyses, only pathologically N-positive tumors (1-3 vs 0 positive lymph nodes: odds ratio [OR], 1.6; 4-9 vs 0 positive lymph nodes: OR, 2.23 [P= .03]) and low-positive ER status (OR, 2.04; P= .01) were associated with recurrence within 2.5 years compared with recurrence between 2.5 years and 5 years. Other clinical and pathologic variables were not predictive of early recurrence. CONCLUSIONS: Subgroups of women with early ER-positive breast cancer may be identified who are at increased risk of recurrence within 2.5 years of diagnosis despite tamoxifen. It remains to be proven whether upfront AI therapy results in an advantage to these women.     

Childhood and adolescent thyroid carcinoma

OBJECTIVES: This analysis was performed to evaluate the influence of clinical and treatment factors on local tumor control, control of distant metastasis, survival, and complications in children and adolescents with thyroid carcinoma. METHODS: The records of 56 children and adolescents with papillary and follicular carcinoma of the thyroid were reviewed. They ranged in age from 4 to 20 years. There were 43 females and 13 males. At diagnosis, 15 (27%) patients had disease confined to the thyroid, 34 (60%) had additional lymph node metastasis to the neck or upper mediastinum, and 7 (13%) also had lung metastasis. Treatment consisted of a total thyroidectomy in 48 patients, a subtotal thyroidectomy in 4 patients, and a lobectomy in 4 patients. All 56 patients received postoperative thyroid hormone suppressive therapy. (131)I was administered to 82% (46 of 56) of patients after their initial surgery. RESULTS: The overall survival rate was 98% with a follow-up of 0.6-30.7 years (with a median follow-up of 11.0 years). The one death that occurred in this patient population was the result of a congenital heart defect and was unrelated to thyroid carcinoma. The 10-year progression-free survival rate was 61%. Nineteen patients (34%) experienced a recurrence of their thyroid carcinoma. The time to first recurrence of disease ranged from 8 months to 14.8 years (mean, 5.3 years). None of those with disease confined to the thyroid developed recurrent disease. The recurrence rate was 50% (17 of 34) in patients with lymph node metastasis and 29% (2 of 7) in patients with lung metastasis (P = 0.02). Tumor characteristics were evaluated for time to first recurrence utilizing the logistic likelihood ratio test to predict disease recurrence. Thyroid capsule invasion (P = 0.02), soft tissue invasion (P = 0.03), positive margins (P = 0.006), and tumor location at diagnosis (thyroid only vs. thyroid and lymph nodes vs. thyroid, lymph nodes, and lung metastasis, P = 0.02) were significant for developing recurrent disease. Patients younger than 15 years old at diagnosis were more likely to have more extensive tumor at diagnosis than patients who were 15 years and older (thyroid only vs. thyroid and lymph nodes vs. thyroid, lymph nodes, and lung metastasis, P = 0.02). CONCLUSION: Carcinoma of the thyroid in children and adolescents has little risk of mortality but a high risk of recurrence. Younger patients present with a more advanced stage of disease and are more likely to have disease recurrence. Total thyroidectomy and lymph node dissection, followed by postoperative (131)I therapy, thyroid hormone replacement (suppressive) administration, and diligent surveillance are warranted.     

A prospective study of concurrent cyclophosphamide/methotrexate/5-fluorouracil and reduced-dose radiotherapy in patients with early-stage breast carcinoma

BACKGROUND: Concurrent administration of chemotherapy and radiotherapy has the potential advantage of delaying neither treatment and providing radiation sensitization. However, the optimal approach to concurrent treatment in women with early-stage breast carcinoma remains undefined. We present updated results of a prospective protocol of concurrent cyclophosphamide/methotrexate/5-fluorouracil (CMF) and reduced-dose radiotherapy, focusing on tumor control and patient tolerance. METHODS: One hundred twelve women with AJCC Stage I or Stage II breast carcinoma with 0-3 positive axillary lymph nodes were enrolled in a prospective single-arm study of concurrent CMF and reduced-dose radiotherapy (39.6 gray [Gy] to the whole breast, 16-Gy boost). A high proportion of women had risk factors associated with an increased risk of local disease recurrence, including age <40 (32%), close or positive margins (37%), or lymphatic/vascular invasion (51%). The median follow-up period was 94 months. RESULTS: The 5-year overall survival rate was 94%. By 60 months, 5 patients (4%) experienced local disease recurrence and 19 patients (17%) experienced distant metastasis. There were no isolated regional lymph node recurrences. Local disease recurrence occurred in 1 of 25 patients (4%), 1 of 16 patients (6%), and 3 of 70 patients (4%) with positive, close (<1 mm), and negative margins, respectively. One patient developed acute myelogenous leukemia. An additional patient developed Grade 2 pneumonitis. Cosmetic results were not recorded uniformly for all patients and therefore could not be reliably analyzed. CONCLUSIONS: Concurrent CMF and reduced-dose radiotherapy resulted in a low level of late toxicity and excellent local tumor control, despite the large proportion of patients with substantial risk factors for local disease recurrence. Future studies of concurrent regimens, particularly in patients at high risk of local disease recurrence, are warranted.     

Natural history of surgically treated bladder carcinoma with extravesical tumor extension

BACKGROUND: The current TNM classification for bladder carcinoma stratifies extravesical extension into microscopic (pT3a) and macroscopic (pT3b) tumor involvement. The authors evaluated the outcomes of patients with pT3a and pT3b disease after radical cystectomy. METHODS: Patients (n = 129) with transitional cell carcinoma of the bladder treated with radical cystectomy alone demonstrated pathologic extravesical tumor extension: 37 (29%) had pT3a disease and 92 (71%) had pT3b disease. No patient received any adjuvant therapy. With a median follow-up of 13.6 years, the presence of lymph node involvement, margin positivity, local (pelvic) and distant disease recurrence, and clinical outcomes were determined. RESULTS: Of the 129 patients, 43 (33%) had lymph node tumor involvement: 13 of 37 patients with pT3a disease (35%) and 30 of 92 patients with pT3b disease (33%). The 10-year recurrence-free and overall survival for the entire group was 54% and 20%, respectively. No statistical difference between pT3a and pT3b disease was observed with regard to recurrence-free (P = 0.54) and overall (P = 0.66) survival. Lymph node involvement was predictive of a significantly worse 10-year recurrence-free survival (32%) compared with lymph node-negative disease (60%; P = 0.003). Local disease recurrence was reported to occur in 12 patients (9%), whereas 37 patients (29%) were reported to develop distant metastases. Among those who had disease recurrence, the type of disease recurrence (local or distant) was not found to be associated with tumor stage (pT3a vs, pT3b, P = 0.47). CONCLUSIONS: This cohort of surgically managed patients provided insight into the long-term natural history of pathologically confirmed extravesical bladder carcinoma after radical cystectomy. There was no important difference in the incidence of lymph node involvement, survival rates, and disease recurrence rates between patients with microscopic and macroscopic extravesical extension. Adjuvant protocols should be undertaken for these high-risk patients to further improve on these clinical outcomes.     

Long-term outcome after postmastectomy radiation therapy for breast cancer patients at high risk for local-regional recurrence

PURPOSE: Postmastectomy radiation therapy is often recommended for patients at high risk for local-regional recurrence after mastectomy. However, long-term outcomes after radiation therapy are not well described. PATIENTS AND METHODS: Between 1977 and 1992, 221 patients at high risk for local-regional recurrence of breast cancer after mastectomy were treated with radiation therapy, with or without adjuvant systemic therapy. Patients were classified as high risk because of T3 or T4 tumors (14%), positive lymph nodes (29%), close or positive margins of resection (15%), or multiple risk factors (39%); 4% did not meet current criteria for radiation therapy. The median age of patients was 51 years. Radiation therapy consisted of 45 to 50.4 Gy to the chest wall in 1.8 to 2.0 Gy fractions. The regional lymph nodes were treated in 187 patients (85%). There were 151 patients (68%) who received adjuvant chemotherapy. Patients who received chemotherapy were younger (median age, 48 years vs 64 years) and had more positive lymph nodes (median, 5 vs 1) than patients not receiving chemotherapy. Adjuvant hormonal therapy was utilized in 116 patients (53%). The median follow-up was 4.3 years. RESULTS: The actuarial 10-year local-regional failure rate was 11% (95% CI: 6.5% to 16.7%). The site of first failure was distant metastases in 75 patients (34%), local-regional recurrence in 11 patients (5%), and both sites in three patients (1%); 60% had no evidence of disease at last follow-up. Of the patients who presented with local-regional recurrence as first failure, nine patients (82%) subsequently developed metastatic disease. The median time to local-regional first failure was 1.3 years. The median time to distant metastases after local-regional first failure was 0.3 years. DISCUSSION: Postmastectomy radiation therapy is associated with an 89% rate of local-regional control in this high-risk population. Patients who experience a local-regional recurrence after radiation therapy are at a very high risk for metastatic disease. Radiation therapy after mastectomy is recommended to optimize local-regional control for high-risk breast cancer patients.     

Survival of patients with metastatic breast carcinoma: importance of prognostic markers of the primary tumor

BACKGROUND: Women with metastatic breast carcinoma have a highly variable clinical course and outcome. Intrinsic genetic heterogeneity of the primary breast tumor may play a role in this variability and may explain it in part. Therefore, the authors tested the hypothesis that the characteristics of primary breast tumors are important determinants of prognosis and survival in patients with metastatic breast carcinoma. METHODS: The prognostic significance of the biology of the primary tumor for outcome in patients with metastatic breast disease was assessed in 346 patients with lymph node positive breast carcinoma who developed distant, recurrent disease. Traditional prognostic indicators (age, tumor size, number of involved lymph nodes, sites of recurrence, disease free interval [DFI], adjuvant treatments, estrogen receptor [ER] expression, progesterone receptor [PgR] expression, S-phase fraction [SPF], and DNA ploidy), together with three newer biologic markers (c-erbB-2, p53, and bcl-2) were assessed. Sites of recurrence were defined as nonvisceral (bone and locoregional lymph nodes) or visceral (lung, liver, brain, and other organs). RESULTS: The median duration of survival was 17.8 months (95% confidence interval, 15.2-21.5 months). Univariate analysis showed that age > 50 years, visceral disease, and shorter DFI were associated significantly with poor outcome (P < 0.05). In addition, the molecular phenotype of the primary breast tumor was significant, with primary tumors that showed ER negativity and PgR negativity, high SPF, aneuploidy, accumulation of p53 protein, and lower bcl-2 expression, together with c-erbB-2 overexpression, all associated with a poorer clinical outcome (P < 0.05). In a multivariate analysis, older age, visceral disease, shorter DFI, PgR negativity, high SPF, and lower bcl-2 expression were significant predictors of worse survival (P < 0.05). CONCLUSIONS: In addition to traditional risk factors, bcl-2 negativity was associated significantly with a worse clinical outcome. Biologic features of primary tumors were correlated independently with outcome after first recurrence in patients with metastatic breast carcinoma and may be used as indicators of prognosis in the metastatic setting.     

Mammographic screening reduces risk of breast carcinoma recurrence

BACKGROUND: The current report is a long-term evaluation of breast carcinoma recurrence, factors predicting recurrence, and postrecurrence prognosis in relation to patients' use of service screening, which has been provided in Turku, Finland, since 1987 for women ages 40-74 years. METHODS: The current study included 527 invasive breast carcinomas: 418 in the screening group (which included screen-detected and interval malignancies) and 109 in the nonscreening group (which included breast carcinomas detected before initial screening and those detected in patients who chose not to undergo screening). These breast carcinomas were diagnosed among women ages 40-74 years between 1987 and 1993, with follow-up extending until the end of 2001. RESULTS: In the screening group, the risk of recurrence was only approximately half of the corresponding risk in the nonscreening group (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.39-0.83; P = 0.003). Five years after the primary diagnosis, 16% of patients in the screening group and 28% of patients in the nonscreening group (P = 0.001) had experienced recurrence; 10 years after diagnosis, the corresponding rates were 21% and 34%, respectively (P = 0.001). Postrecurrence prognosis was comparable for both detection groups (HR, 1.17; 95% CI, 0.70-1.94; P = 0.551), with approximately half of all patients dying of disease 5 years after recurrence. Detection of breast carcinoma via a method other than mammographic screening was associated with a high risk of recurrence on univariate analysis. On Cox multivariate analysis, risk factors for recurrence included lobular histologic type (HR, 2.23; 95% CI, 1.44-3.48; P < 0.001), poor histologic grade (HR, 2.02; 95% CI, 1.20-3.39; P = 0.008), and large tumor size (HR, 1.60; 95% CI, 1.07-2.37; P = 0.021). CONCLUSIONS: Long-term data from a population-based program demonstrated that mammographic screening reduced patients' risk of breast carcinoma recurrence. Specifically, the risk for patients with screen-detected disease was only approximately half of the risk for patients with non-screen-detected disease. Nonetheless, postrecurrence prognosis was comparable for patients in both detection groups.     

The prognostic significance of the percentage of positive/dissected axillary lymph nodes in breast cancer recurrence and survival in patients with one to three positive axillary lymph nodes

BACKGROUND: Adjuvant therapy for women with T1-T2 breast carcinoma and 1-3 positive lymph nodes is controversial due to discrepancies in reported baseline locoregional recurrence (LRR) risks. This inconsistency has been attributed to variations in lymph node staging techniques, which have yielded different numbers of dissected lymph nodes. The current study evaluated the prognostic impact of the percentage of positive/dissected lymph nodes on recurrence and survival in women with one to three positive lymph nodes. METHODS: The study cohort was comprised of 542 women with pathologic T1-T2 breast carcinoma who had 1-3 positive lymph nodes and who had undergone mastectomy and received adjuvant systemic therapy without radiotherapy. Ten-year Kaplan-Meier (KM) LRR, distant recurrence (DR), and overall survival (OS) rates stratified by the number of positive lymph nodes, the number of dissected lymph nodes, and the percentage of positive lymph nodes were examined using different cut-off levels. Multivariate analysis was performed to evaluate the prognostic significance of the percentage of positive lymph nodes in disease recurrence and survival. RESULTS: The median follow-up was 7.5 years. LRR, DR, and OS rates correlated significantly with the number of positive lymph nodes and the percentage of positive lymph nodes, but not with the number of dissected lymph nodes. The cut-off level at which the most significant difference in LRR was observed was 25% positive lymph nodes (the 10-year KM LRR rates were 13.9% and 36.7% in women with < or = 25% and > 25% positive lymph nodes, respectively; P < 0.0001). Higher DR rates and lower OS rates were observed among patients who had > 25% positive lymph nodes compared with patients who had < or = 25% positive lymph nodes (DR: 53.0% vs. 30.3%, respectively; P < 0.0001; OS: 43.4% vs. 62.6%, respectively; P < 0.0001). In the multivariate analysis, the percentage of positive lymph nodes and the histologic grade were significant, independent factors associated with LRR, DR, and OS. CONCLUSIONS: The presence of > 25% positive lymph nodes was an adverse prognostic factor in patients with 1-3 positive nodes and may be used to identify patients at high risks of postmastectomy locoregional and distant recurrence who may benefit with adjuvant radiotherapy and more aggressive systemic therapy regimens.     

Thyroid hormone and breast carcinoma. Primary hypothyroidism is associated with a reduced incidence of primary breast carcinoma

BACKGROUND: To investigate the role of primary hypothyroidism (HYPT) on breast carcinogenesis, the authors evaluated 1) the association between HYPT and a diagnosis of invasive breast carcinoma and 2) the clinicopathologic characteristics of breast carcinoma in patients with HYPT. METHODS: For this retrospective chart review study, 1136 women with primary breast carcinoma (PBC) were identified from the authors' departmental data base. These women (cases) were frequency-matched for age (+/- 5 years) and ethnicity with 1088 healthy participants (controls) who attended a breast carcinona screening clinic. Women with HYPT who were receiving thyroid-replacement therapy before they were diagnosed with breast carcinoma or before the screening visit were identified. RESULTS: The mean ages of cases and controls (51.6 years vs. 51.0 years, respectively; P = 0.30) and their menopausal status (65.4% premenopausal vs. 62% postmenopausal; P = 0.10) were comparable. Two hundred forty-two women in the case group (10.9%) with HYPT were identified. The prevalence of this condition was significantly greater the control group compared with the case group (14.9% vs. 7.0%, respectively; P < 0.001). PBC patients were 57% less likely to have HYPT compared with their healthy counterparts (odds ratio, 0.43l 95% confidence interval, 0.33-0.57). Seventy-eight white patients with PBC had HYPT and, compared with women who were euthyroid, they were older at the time of diagnosis (58.8 years vs. 51.1 years; P < 0.001), were more likely to have localized disease (95.0% vs. 85.9% clinical T1 or T2 disease, respectively; P = 0.025), and were more likely to have no pathologic lymph node involvement (62.8% vs. 54.4%; P = 0.15). CONCLUSIONS: Primary HYPT was associated with a reduced risk for PBC and a more indolent invasive disease. These data suggest a possible biologic role for thyroid hormone in the etiology of breast carcinoma and indicate areas of research for the prevention and treatment of breast carcinoma.     

Significance of axillary lymph node extranodal soft tissue extension and indications for postmastectomy irradiation.

BACKGROUND: Extranodal soft tissue extension of axillary lymph node metastases (ETE) has been considered an indication for postmastectomy radiotherapy, including the axilla. However, it is unclear whether patients with ETE are at an increased risk of axillary recurrence. METHODS: From a single institutional database of 2362 patients with breast carcinoma treated between 1974-1994, a total of 487 patients who underwent mastectomy for lymph node positive, infiltrating (T1-T3) breast carcinoma was found. All the patients had pathologically confirmed axillary lymph node metastases and negative surgical margins; none had received postoperative irradiation. Of these patients, 50 had histologically documented axillary ETE. Forty-three patients had a minimum follow-up of at least 1 year and comprise the study population. The median follow-up time of surviving ETE positive patients was 79 months. Twenty-five patients (58.1%) received adjuvant systemic therapy. Sites of first failure were local or distant. Local failure was categorized further as chest wall failure, axillary failure, supraclavicular lymph node failure, or internal mammary lymph node failure. RESULTS: For the 43 patients with ETE, the median patient age was 59.5 years (range, 38-81 years) and the median tumor size was 3.6 cm (range, 0.5-12.0 cm). The median number of positive axillary lymph nodes was 6 (range, 1-36 lymph nodes) versus 2 (range, 1-30 lymph nodes) for all T1-T3 ETE positive patients compared with ETE negative patients (P < 0. 001). The risk of ETE increased significantly with increasing numbers of axillary lymph node metastases (P < 0.001). Of the patients with ETE, 16 (37.2%) developed recurrent disease. ETE positive patients with disease recurrence had significantly greater numbers of positive axillary lymph nodes (median, 10 lymph nodes) than those patients who were recurrence free (median, 4 lymph nodes) (P = 0.02). The site of first failure was local in 7 patients (16. 3%) and distant in 9 patients (20.9%). All patients with local recurrence had chest wall failures; there were no isolated lymph node recurrences. The only simultaneous local and distant failure was in one patient presenting with supraclavicular and intraabdominal metastases. CONCLUSIONS: The risk of axillary recurrence, either as an isolated event or as part of simultaneous failure, is extremely low, even in patients with ETE. These data suggest that patients with ETE frequently have higher numbers of positive axillary lymph nodes and on that basis are at risk for local recurrence and as a rule would be considered for postmastectomy irradiation. However, these data suggest that the presence of ETE is not an indication for routine postmastectomy axillary lymph node irradiation.     

Prognostic significance of BRCA1 expression in Japanese sporadic breast carcinomas.

BACKGROUND: BRCA1 is a tumor suppressor gene that is responsible for hereditary breast and ovarian carcinoma syndrome. The primary objective of the current study was to investigate the influence of BRCA1 expression on the prognoses of sporadic breast carcinomas. METHODS: A cohort of 175 Japanese women with invasive breast carcinoma who had no family history in first-degree relatives was studied. Expression of BRCA1 was determined by an immunohistochemical procedure in which the MS110 monoclonal antibody was used. Kaplan--Meier and Cox proportional regression survival analyses were used to compare negative and positive BRCA1 patients. RESULTS: One hundred fifteen (65.7%) of the 175 specimens showed positive BRCA1 staining (> 10% cells were immunoreactive). During a median follow-up of 4.4 years, negative BRCA1 patients had worse disease free survival than positive BRCA1 patients (35 % vs. 7%, respectively; P < 0.0001). BRCA1 expression was significantly inversely correlated with histologic grade (P < 0.0001) but not with lymph node status or other conventional prognostic markers. In multivariate analysis using the Cox regression model, positive BRCA1 emerged as an independent prognostic indicator for disease free survival. CONCLUSIONS: The results of this study suggest that BRCA1 may be a valuable marker for identifying women with sporadic breast carcinoma at high risk of developing recurrence, and who may be candidates for trials investigating new therapies in combination with standard adjuvant therapy.     

乳腺纯上皮化生性癌9例观察及文献复习

背景与目的:乳腺化生性癌十分少见。对此,本文旨在探讨乳腺纯上皮化生性癌的病理和临床特征以及治疗。方法:回顾性分析1997-2007年9例在我院治疗的女性乳腺纯上皮化生性癌病例。结果:患者中位年龄50岁(37～78岁),9例均行根治术或改良根治术,病理诊断为梭形细胞化生性癌6例,鳞癌3例。雌激素受体(ER)和/或孕激素受体(PR)阳性者2例。2例淋巴结转移。中位随访时间为25(3～112)个月,术后局部复发1例,远处转移3例,肺转移2例,2例患者死亡,1例带瘤生存。结论:本病以梭形细胞化生性癌多见,可同时表达上皮和间叶组织抗原,但较少表达ER和PR。患者多以无痛性肿块就诊,肿块局切复发率高。腋窝淋巴结转移少见,肺转移多见。手术治疗宜选择单纯乳房切除加前哨淋巴结活检。     

Sentinel lymph node biopsy in patients with male breast carcinoma

BACKGROUND: Sentinel lymph node biopsy (SLNB) is now a widely implemented technique for evaluating the axilla in women with early stage breast carcinoma. Men who develop breast carcinoma are at similar risk as their female counterparts of developing the morbidities related to axillary dissection. SLNB is aimed at preventing these morbidities. In this study, the authors evaluated the role of SLNB in the treatment of men with early stage breast carcinoma. METHODS: Among the 1692 patients who underwent SLNB at the Memorial Sloan-Kettering Cancer Center, 16 men with breast carcinoma were identified. The charts and records of these 16 patients were reviewed retrospectively. RESULTS: The mean patient age was 57.2 years. The mean tumor size was 1.3 cm. In 15 of 16 patients (93.75%) and in all patients with T1 tumors, one or more sentinel lymph nodes were successfully identified. SLNB failed in one patient, who had a T2 tumor (3 cm). Ten of the 15 patients had negative sentinel lymph nodes (66.7%). Four of these patients had no additional lymph nodes removed, whereas six patients had additional lymph nodes removed, all of which were negative. Two patients (13.3%) had positive sentinel lymph nodes on frozen-section analysis and underwent immediate completion axillary dissection: Both had additional positive lymph nodes. Three patients (20.0%) had positive sentinel lymph nodes on further sectioning or immunohistochemistry, and two patients underwent completion axillary dissection: Neither patient had additional positive lymph nodes. The third patient had one immunohistochemically positive lymph node and did not undergo completion axillary dissection. CONCLUSIONS: SLNB for patients with breast carcinoma was as successful in men as it has been shown to be in women and may be offered as a management option to men with early stage breast carcinoma by surgeons who are experienced with the technique.     

Lobular carcinoma in situ increases the risk of local recurrence in selected patients with stages I and II breast carcinoma treated with conservative surgery and radiation

BACKGROUND: Lobular carcinoma in situ (LCIS) is a known risk factor for the development of invasive breast carcinoma. However, little is known regarding the impact of LCIS in association with an invasive carcinoma on the risk of an ipsilateral breast tumor recurrence (IBTR) in patients who are treated with conservative surgery (CS) and radiation therapy (RT). The purpose of this study was to examine the influence of LCIS on the local recurrence rate in patients with early stage breast carcinoma after breast-conserving therapy. METHODS: Between 1979 and 1995, 1274 patients with Stage I or Stage II invasive breast carcinoma were treated with CS and RT. The median follow-up time was 6.3 years. RESULTS: LCIS was present in 65 of 1274 patients (5%) in the study population. LCIS was more likely to be associated with an invasive lobular carcinoma (30 of 59 patients; 51%) than with invasive ductal carcinoma (26 of 1125 patients; 2%). Ipsilateral breast tumor recurrence (IBTR) occurred in 57 of 1209 patients (5%) without LCIS compared with 10 of 65 patients (15%) with LCIS (P = 0.001). The 10-year cumulative incidence rate of IBTR was 6% in women without LCIS compared with 29% in women with LCIS (P = 0.0003). In both groups, the majority of recurrences were invasive. The 10-year cumulative incidence rate of IBTR in patients who received tamoxifen was 8% when LCIS was present compared with 6% when LCIS was absent (P = 0.46). Subsets of patients in which the presence of LCIS was associated with an increased risk of breast recurrence included tumor size < 2 cm (T1), age < 50 years, invasive ductal carcinoma, negative lymph node status, and the absence of any adjuvant systemic treatment (chemotherapy or hormonal therapy) (P < 0.001). LCIS margin status, invasive lobular carcinoma histology, T2 tumor size, and positive axillary lymph nodes were not associated with an increased risk of breast recurrence in these women. CONCLUSIONS: The authors conclude that the presence of LCIS significantly increases the risk of an ipsilateral breast tumor recurrence in certain subsets of patients who are treated with breast-conserving therapy. The risk of local recurrence appears to be modified by the use of tamoxifen. Further studies are needed to address this issue.     

Are older breast carcinoma survivors willing to take hormone replacement therapy?

BACKGROUND: Breast carcinoma survivors are the largest segment of the expanding cancer survivor community. As a result, there has been increasing discussion of the safety and efficacy of hormone replacement therapy for women with a past history of breast carcinoma. Little is known about the willingness of older breast carcinoma survivors to accept hormone replacement therapy for the alleviation of menopausal symptoms (such as hot flashes, vaginal dryness, and urinary incontinence) or for reduction in the risk of serious heart disease or osteoporotic hip fracture. METHODS: A structured decision analysis interview was conducted, in which visual aids were used to describe therapy and hypothetical risks of breast carcinoma recurrence. Subjects were presented with a series of scenarios in which a hypothetical woman might be experiencing one of several menopausal symptoms or might have a reduction in the risk of serious heart disease or osteoporotic hip fracture. RESULTS: Thirty-nine disease free breast carcinoma survivors who were age 60 years or older were recruited to participate in a study that included interview and physical examination. Subjects were age 68.3 years on average and had been diagnosed with breast carcinoma an average of 3.1 years previously. The majority had received hormone replacement therapy at some point in the past. They showed high levels of functioning as measured by the RAND Short Form Health Survey. Willingness to take estrogen was evident only when the increase in the risk of breast carcinoma recurrence was small and when severe symptoms of menopause were present. Under the hypothetical conditions of this interview, 56.4% of these 39 breast carcinoma survivors would be willing to take estrogen if they had all 3 menopausal symptoms and their risk of breast carcinoma recurrence increased from 25% to 32%. In contrast, for the osteoporosis and heart disease scenarios (in which women were as yet asymptomatic), only 17.9% were willing to take estrogen to reduce the risk of hip fracture by 50% and only 28.2% were willing to take estrogen to reduce the risk of heart attack by 50% under the same assumption of a 7% difference in the risk of recurrence (from 25% to 32%). CONCLUSIONS: Overall, the study findings demonstrate the reluctance of these older breast carcinoma survivors to take estrogen after a breast carcinoma diagnosis. There was an increased willingness to consider therapy if multiple symptoms coexisted and the possible risk of recurrence was small (13% compared with 10%). There was also no significant correlation between current menopausal symptoms and the willingness to take estrogen in the hypothetical situations posed in the interview. These findings suggest an important feasibility problem that must be addressed before hormone replacement clinical trials involving breast carcinoma survivors are launched.     

Pregnancy after breast carcinoma: outcomes and influence on mortality.

BACKGROUND: To the authors' knowledge, no previous studies have identified an adverse effect of pregnancy on patient survival after breast carcinoma. However, results are difficult to interpret because of failure to control for stage of disease at the time the pregnancy occurred. METHODS: Study participants were women diagnosed with invasive breast carcinoma between 1983-1992 who previously had participated in a population-based case-control study or, if deceased, proxy respondents. Information regarding subsequent pregnancies was obtained by self-administered questionnaire or telephone interview. Information regarding breast carcinoma recurrences was obtained by questionnaire and from cancer registry abstracts. Women who became pregnant after a diagnosis of breast carcinoma (n = 53) were matched with women without subsequent pregnancies based on stage of disease at diagnosis and a recurrence free survival time in the comparison women greater than or equal to the interval between breast carcinoma diagnosis and onset of pregnancy in the women with a subsequent pregnancy. RESULTS: Sixty-eight percent of women who became pregnant after being diagnosed with breast carcinoma delivered one or more live-born infants. Miscarriages occurred in 24% of the patients who became pregnant compared with 18% of the controls (women without breast carcinoma) of similar ages from the case-control study. Five of the 53 women who had been pregnant after breast carcinoma died of the disease. The age-adjusted relative risk (RR) of death associated with any subsequent pregnancy was 0.8 (95% confidence interval [95% CI], 0.3-2.3). All five deaths occurred among the 36 women who had a live birth (age-adjusted RR = 1.1; 95% CI, 0.4-3.7). CONCLUSIONS: The findings of the current study are based on a small number of deaths but do not suggest that pregnancy after a diagnosis of breast carcinoma has an adverse effect on survival.     

Long-term outcomes and clinicopathologic differences of African-American versus white patients treated with breast conservation therapy for early-stage breast cancer

BACKGROUND: African-American (AA) and white patients with early-stage disease who were treated with breast conservation therapy (BCT) were examined to detect differences in clinicopathologic features and outcomes as a function of race. METHODS: Clinical data from the charts of 2164 white and 207 AA patients treated with BCT, and p53 expression status on 444 patients (from an existing tissue database), were analyzed to detect differences between the 2 cohorts. RESULTS: The median follow-up was 7 years. There were no differences in the method of tumor detection, lymph nodes excised, surgical margin status, or chemotherapy/radiotherapy delivered, reflecting similar screening and treatment policies for AA women in the study community. Despite this, AA patient presented at a younger age, with higher T and N classifications, and more estrogen and progesterone negative and "triple negative" tumors (all P values < .016). Tumors in AA patients were p53 positive more often than tumors in white patients (P= .0003). At 10 years, AA patients had a higher rate of distant metastasis (20% vs 17%; P= .042), lymph node recurrence (6% vs 2%; P= .004), and breast recurrence (17% vs 13%; P= .036). There was no difference in overall survival between the 2 groups. On multivariate analysis, only lymph node recurrence (risk ratio of 3.140; 95% confidence interval, 1.396-7.063 [P= .0057]) remained significantly higher among AA women. CONCLUSIONS: In this cohort of uniformly treated patients, the authors found the expected clinicopathologic differences, but race was not found to be an independent predictor of local recurrence for AA patients when other confounding variables were taken into account in the multivariate model. These findings suggest that BCT is a reasonable option for appropriately selected AA patients. To the authors' knowledge, this is the largest study addressing outcomes after BCT for AA women published to date.     

The effect of less than definitive care on breast carcinoma recurrence and mortality

BACKGROUND: Risk factors for breast carcinoma offer few opportunities for prevention; thus, the reduction of morbidity and mortality among breast carcinoma patients must remain a priority. The objective of this study was to measure the effects of less than definitive care for patients with breast carcinoma on disease recurrence and mortality. METHODS: The prognostic evaluation and treatment received by an inception cohort of 494 women was characterized. Three hundred ninety women ages 45-90 years with local or regional breast carcinoma who were diagnosed between 1984 and 1986 and were treated at one of eight Rhode Island hospitals comprised the final cohort. Disease recurrence and mortality were ascertained through December 31, 1996. Candidate determinants of outcomes were a less than definitive prognostic evaluation and less than definitive primary therapy-adjusted for confounding by patient age, extent of disease, and comorbid diseases. RESULTS: During the first 5 years of follow-up, patients who received a less than definitive prognostic evaluation had an adjusted relative hazard of recurrence of 1.7 (95% confidence interval, 1.0-2.7) and an adjusted relative hazard for breast carcinoma mortality of 2.2 (95% confidence interval, 1.2-3.9). Patients who received less than definitive therapy had an adjusted relative hazard of recurrence of 1.6 (95% confidence interval, 1.0-2.5), and an adjusted relative hazard of breast carcinoma mortality of 1.7 (95% confidence interval, 1.0-2.8). CONCLUSIONS: Breast carcinoma patients who receive less than definitive care are at excess risk for disease recurrence and mortality. Women with early stage breast carcinoma should be treated in accordance with existing guidelines.