Risk of breast cancer in female survivors of childhood Hodgkin's disease in Britain: a population-based study

There is now widespread evidence that female survivors of Hodgkin's disease who have been treated with supradiaphragmatic radiotherapy are at an increased risk of breast cancer. Mantle irradiation, which includes irradiation of the mediastinum, conveys a particularly high risk. Previously published studies have found a wide variation in risk. To provide British estimates of risk to inform surveillance programmes, we carried out the first British population-based cohort study of breast cancer in female survivors of childhood Hodgkin's disease. From the underlying cohort of the British Childhood Cancer Survivor Study, a cohort of 18,123 British 5-year survivors of childhood cancer diagnosed between 1940 and 1991, there were in total 383 female 5-year survivors of childhood Hodgkin's disease. Sixteen of these 383 survivors went on to develop invasive breast cancer subsequent to 5-year survival (standardised incidence ratio, 11.5; 95% confidence interval (95% CI), 6.6-18.6) and all of these 16 survivors had been treated with supradiaphragmatic irradiation as treatment for childhood Hodgkin's disease. The cumulative risk of breast cancer by 25 years of follow up was 9.9% (95% CI, 3.3-16.6) for all patients and 12.2% (95% CI, 4.3-20.1) for those treated with supradiaphragmatic radiotherapy. The cumulative risk of breast cancer in female survivors of childhood Hodgkin's disease in Britain is at the lower end of previous estimates. We hope that our data may provide a basis for future surveillance and for counselling survivors as to their likely risk of breast cancer.     

Prognostic factors in patients with isolated recurrences of breast cancer (stage IV-NED)

Background: One to 10% of women with metastatic breast cancer have a recurrence of their disease as an isolated lesion (local, regional, or distant) which may be treated by surgical resection, irradiation, or both. These are patients with stage IV breast cancer with no evidence of disease, or stage IV-NED. Because natural history and prognostic factors for patients with stage IV-NED are poorly determined, we decided to evaluate a group of patients with stage IV-NED treated at a single institution.Patients and methods: Ninety-six patients with isolated recurrence of stage IV breast cancer were analyzed retrospectively. Treatment of loco-regional or distant recurrence was surgery in 18 patients and surgery plus irradiation in 78 patients. Seventy-nine patients received systemic therapy after loco-regional treatment (24 chemotherapy and 55 hormonotherapy). Prognostic factors were analyzed and correlated with disease-free survival (DFS) and overall survival (OS).Results: Five-year DFS and OS for the whole group were 29% and 49% respectively. On the univariate analysis, patients without axillary nodal involvement at the time of mastectomy had significantly greater 5-year DFS and OS than patients with nodal involvement (51% vs. 14% and 70% vs. 34% respectively, p< 0.05). DFS was also significantly better for patients receiving systemic therapy after local treatment (31% vs. 19%). On the multivariate analysis, absence of nodal involvement and systemic therapy were associated with longer DFS (p = 0.044 and p = 0.008, respectively) and OS (p = 0.009 and p = 0.011, respectively). None of the other factors analyzed including menopausal status, T-stage, number of involved nodes, receptor status, adjuvant therapy, sites of first recurrence, or time from mastectomy to first recurrence had a predictive value for DFS and OS.Conclusion: Patients with stage IV-NED have poor prognosis due to early development of metastatic disease. Absence of axillary nodal involvement at the time of mastectomy and systemic therapy following local management is associated with improved DFS and OS. These results suggest that systemic therapy after local treatment in stage IV-NED is indicated. Poor prognosis in patients with previous nodal involvement warrants new approaches.     

The therapeutic implications of splenic involvement in stage IIIA Hodgkin's disease.

In an effort to determine the most appropriate initial therapy for patients with stage IIIA Hodgkin's disease, a comparative analysis was undertaken of 13 pathologically staged IIIA Hodgkin's disease patients whose abdominal disease was localized to the spleen (IIIsA); 17 IIIA patients with spleen and abdominal lymph node involvement (IIIs+n+A) and 44 stage IIA patients. The three groups were treated concurrently with either extended field irradiation alone or limited field irradiation followed by MOPP chemotherapy. Relapse rates after irradiation alone were 17% for the IIIsA patients; 63% for the IIIs+n+A patients and 25% for the stage IIA patients. Following therapy with irradiation and chemotherapy no relapses occurred among the IIIsA and IIIs+n+A patients while 2/16 (13%) stage IIA patients relapsed. After irradiation alone stage IIIs+n+A patients had a significantly shorter remission duration and survival than the stage IIA patients (p = 0.03 and 0.002, respectively) but remission duration and survival were similar for the IIIsA and IIA patients. When therapy was irradiation and chemotherapy no significant differences in remission duration or survival were noted for the three groups. The most common sites of relapse for the IIIs+n+A patients were extralymphatic (60%) while no extralymphatic relapse have occurred among the IIIA patients (p less than 0.02). The only relapse among the IIIsA patients was at an extralymphatic site. These data have shown that patients with IIIsA Hodgkin's disease have a similar prognosis to stage IIIA disease but after therapy with irradiation along stage IIIs+n+A patients have a poorer prognosis. Combined irradiation and chemotherapy should, therefore, be considered for stage IIIs+n+A Hodgkin's disease when abdominal nodal disease cannot be included in the initial radiation port.     

High Tumour Stage and Margin Clearance are Still Important Prognostic Factors for Post-Mastectomy Locoregional Recurrence in Malaysia

Background: Locoregional recurrence after mastectomy for breast cancer may predict distant recurrence andmortality. This study examined the pattern and rates of post-mastectomy locoregional recurrence (PMLRR),survival outcome and prognostic factors for isolated PMLRR (ILR) in a breast cancer cohort in University ofMalaya Medical Center (UMMC). Methods: We studied 522 patients who underwent mastectomy between 1998and 2002 and followed them up until 2008. We defined PMLRR as recurrence to the axilla, supraclavicular nodesand or chest wall. ILR was defined as PMLRR occurring as an isolated event. Prognostic factors for locoregionalrecurrence were determined using the Cox proportional hazards regression model. Results: The overall PMLRRrate was 16.4%. ILR developed in 42 of 522 patients (8.0%). Within this subgroup, 25 (59.5%) remained diseasefree after treatment while 17 (40.5%) suffered disease progression. Univariate analyses identified race, age,size, stage, margin involvement, lymph node involvement, grade, lymphovascular invasion and ER status asprobable prognostic factors for ILR. Cox regression resulted in only Stage III disease and margin involvementas independent prognostic factors. The hazard of ILR was 2.5 times higher when the margins were involvedcompared to when they were clear (aHRR 2.5; 95% CI 1.3 to 5.0). Similarly, compared with stage I those withStage II (aHRR 2.1; 95%CI 0.6 to 6.8) and stage III (aHRR 4.6; 95%CI 1.4 to 15.9) had worse prognosis for ILR.Conclusion: Margin involvement and Stage III disease were identified to be independent prognostic factors forILR. Close follow-up of high risk patients and prompt treatment of locoregional recurrence were recommended.     

Malignant breast tumors after radiotherapy for a first cancer during childhood.

PURPOSE: To assess the specific role of treatment and type of first cancer (FC) in the risk of long-term subsequent breast cancer (BC) among childhood cancer survivors. PATIENTS AND METHODS: In a cohort of 1,814 3-year female survivors treated between 1946 and 1986 in eight French and English centers, data on chemotherapy and radiotherapy were collected. Individual estimation of radiation dose to each breast was performed for the 1,258 patients treated by external radiotherapy; mean dose to breast was 5.06 Gy (range, 0.0 to 88.0 Gy) delivered in 20 fractions (mean). RESULTS: Mean follow-up was 16 years; 16 patients developed a clinical BC, 13 after radiotherapy. The cumulative incidence of BC was 2.8% (95% CI, 1.0% to 4.5%) 30 years after the FC and 5.1% (95% CI, 2.1% to 8.2%) at the age of 40 years. The annual excess incidence increased as age increased, whereas the standardized incidence ratio decreased. On average, each Gray unit received by any breast increased the excess relative risk of BC by 0.13 (< 0.0 to 0.75). After stratification on castration and attained age, and adjusting for radiation dose, FC type, and chemotherapy, a higher risk of a subsequent BC was associated with Hodgkin's disease (relative risk, 7.0; 95% CI, 1.4 to 30.9). CONCLUSION: The reported high risk of BC after childhood Hodgkin's disease treatment seems to be due not only to a higher radiation dose to the breasts, but also to a specific susceptibility.     

Breast cancer after mantle irradiation for Hodgkin's disease: correlation of clinical, pathologic, and molecular features including loss of heterozygosity at BRCA1 and BRCA2

PURPOSE: Hodgkin's disease patients who receive mantle irradiation have an age-dependent increased risk of developing breast cancer. To determine if genetic factors predispose these patients to develop breast cancer, we evaluated breast cancer specimens for loss of heterozygosity (LOH) at regions where BRCA1 and BRCA2, two breast cancer tumor suppressor genes, are located. We also evaluated whether breast cancers in patients who were previously treated with radiation have a more aggressive phenotype, and whether the clinical course differed from a sporadic group of breast cancer patients. METHODS AND MATERIALS: All females with Hodgkin's disease who were subsequently diagnosed with breast cancer and for whom tissue blocks were available were included. Using a case-control design, case patients (previously treated with radiation therapy) were matched with sporadic control breast cancer patients for age, breast cancer stage, and date of breast cancer diagnosis. After microdissection of tumor and normal tissue from paraffin-embedded tissue blocks, DNA was extracted and samples were examined for LOH at chromosomal segments encompassing BRCA1 and BRCA2. Breast cancer specimens were also evaluated in a blinded fashion for tumor grade and immunoreactivity to estrogen and progesterone receptors, p53, her2-neu, and topoisomerase II alpha. Comparisons were made between the case and control populations using chi2 analysis, and a paired Student's t test. Survival differences were evaluated using a log-rank test. RESULTS: From January 1960 to December 1983, 917 patients were diagnosed with Hodgkin's disease. Twelve patients were subsequently diagnosed with breast cancer and tissue blocks were available on 10 cases. No statistical difference was observed between the case and control populations for LOH at BRCA1 or BRCA2. In the Hodgkin's disease group, LOH was observed in 30% of tumors at BRCA1 and 10% of tumors at BRCA2 vs. 10% and 0% of tumors in the control group at BRCA1 and BRCA2, respectively. Breast tumors from patients who received radiation therapy for Hodgkin's disease displayed greater nuclear pleomorphism (p < 0.02), and an increase in topoisomerase II alpha expression (p < 0.05) vs. the control population. Five of 10 patients were pregnant at the time of their Hodgkin's treatment, and those patients had a shorter time interval to the development of breast cancer compared with the patients who were not pregnant (12.4 years compared with 18.6 years). There was no significant difference in disease-free survival; however, overall survival was inferior in the population previously treated with radiation therapy for Hodgkin's disease (p = 0.01). 80% of patients with a previous Hodgkin's diagnosis died of breast cancer or treatment related effects vs. 30% in the control group. CONCLUSION: We were unable to find statistical evidence for LOH at BRCA1 and BRCA2 in breast cancers from patients previously irradiated for Hodgkin's disease. Breast cancer diagnosed after mantle irradiation may be more biologically aggressive based on the greater nuclear pleomorphism and increase in topoisomerase II alpha staining. This did not translate into a statistical difference in breast cancer disease-free survival; however, overall survival was significantly inferior in the Hodgkin's disease patients.     

Does radiotherapy around the time of pregnancy for Hodgkin's disease modify the risk of breast cancer?

PURPOSE: To determine whether the risk of secondary breast cancer after radiotherapy (RT) for Hodgkin's disease is greater among women who underwent RT around time of pregnancy. METHODS AND MATERIALS: The records of 382 women treated with RT for Hodgkin's disease were reviewed and divided into those who received RT around the time of pregnancy and those who were not pregnant. Comparisons of the overall incidence, actuarial rates, and latency to breast cancer between the two groups were made. Multivariate Cox regression modeling was performed to determine possible contributing factors. RESULTS: Of the 382 women, 14 developed breast cancer (3.7%). The increase in the overall incidence (16.0% vs. 2.3%, p = 0.0001) and the actuarial rate of breast cancer among the women in the pregnant group (p = 0.011) was statistically significant. The women treated around the time of pregnancy had a 10- and 15-year actuarial rate of breast cancer of 6.7% and 32.6%, respectively. The 10-year and 15-year actuarial rate for the nonpregnant women was 0.4% and 1.7%, respectively. The median latency from RT to the diagnosis of breast cancer was 13.1 and 18.9 years for women in the pregnant and nonpregnant groups, respectively. In the multivariate analysis, pregnancy around the time of RT was the only variable associated with an increased risk of breast cancer. The risk was dependent on the length of time from pregnancy to RT, with women receiving RT during pregnancy and within 1 month of pregnancy having an increased risk of breast cancer compared with nonpregnant women and women irradiated later than 1 month after pregnancy (hazard ratio, 22.49; 95% confidence interval, 5.56-90.88; p <0.001). CONCLUSION: The results of this study indicate that the risk of breast cancer after RT is greater with irradiation around the time of pregnancy. This suggests that pregnancy is a time of increased sensitivity of breast tissue to the carcinogenic effects of radiation. Because of the small sample size and limited follow-up, additional studies are recommended to confirm these findings.     

Second primary in the contralateral breast after treatment of breast cancer.

PURPOSE: To study the potential risk factors for contralateral breast cancer (CBC) in women after treatment of the primary breast cancer. PATIENTS AND METHODS: Between January 1985 and December 1995, records of 1084 breast cancer patients at our institution were analyzed for incidence of CBC. In all the patients a detailed analysis was carried out with respect to age, disease stage, radiation therapy technique, dose, the use of chemotherapy or hormone therapy, and other clinical and/or pathologic characteristics. The Kaplan-Meier method was used to estimate the acturial rate of CBC. The Cox proportional hazard regression model was used to estimate the relative risk (RR) of CBC. RESULTS: Up to December 2005, the median follow up was 12 years. Overall incidence of CBC was 4%. The 10 and 20 year acturial rate of CBC was 5.6% and 11.3%, respectively. The CBC rate at 10 and 20 year was 5.4% and 10.2%, respectively, for patients with mastectomy only and 5.1% and 9.7%, respectively, in the mastectomy plus RT group (p=0.3). In the subset of patients <45 years of age at the time of treatment, 10 and 20 year acturial rate of CBC was 5% and 9%, respectively, for patients who underwent mastectomy only and 6.3% and 11%, respectively, for patients treated with mastectomy plus RT (RR=1.4, 95% CI: 1.14-1.45, p=0.003). There was statistically significant lower rate of CBC in patients given adjuvant hormonal therapy (8.5%) as compared to those without hormonal therapy (14.3%, p=0.004) at 20 year. Women with family history of breast cancer had highest rate (15.3%) of CBC (RR=1.6, 95% CI: 1.12-1.27) at 20 years. The adjuvant use of chemotherapy did not significantly affect the risk of second malignancy. CONCLUSION: There seems to be little risk of second malignancies in patients treated with mastectomy plus RT using modern techniques, compared with mastectomy only, that was only prevalent in patients <45 years of age. Family history of breast cancer seems to be the highest risk factor for CBC.     

Immediate breast reconstruction with latissimus dorsi flap for patients with local recurrence of breast cancer

BackgroundIpsilateral breast cancer recurrence (IBTR) occurs in about 7% of patients with primary invasive breast tumor. Salvage mastectomy and breast reconstruction are often discussed and latissimus dorsi (LD) flap is frequently proposed.MethodsWe retrospectively investigated 111 consecutive locally relapsing patients who underwent salvage mastectomy and immediate LD reconstruction. All included patients with IBTR previously underwent conserving surgery for BC, and received a postoperative irradiation. Primary endpoints were disease free survival and overall survival. Secondary endpoints were surgical complications and re-interventions.ResultsInvasive ductal cancer was the most frequent histotype (60.4%) of breast cancer reappearance. rpT1, rpT2 and rpT3 were observed respectively in 50.5%, 20,7% and 3,6% of the patients. rpTis occurred in 11,7% of cases. Positive axillary nodes were observed in 9,9% of patients at reappearance. Post-operative complication other than seroma occurred in 17,1% of patients, while seroma at the donor site was observed in 61.3% of cases. At 5-year after surgery overall survival was 92% (95% CI: 85%–96%) and disease free survival was 78% (95% CI: 69%–85%).ConclusionsImmediate latissimus dorsi flap reconstruction in selected patients with isolated breast tumor recurrence, which occurred after breast irradiation, provides an effective treatment with a satisfactory outcome.     

Results of mastectomy and postoperative irradiation in the management of locoregionally advanced carcinoma of the breast

Between 1955 and 1984, 376 patients with locoregionally advanced breast carcinoma were treated at The University of Texas M. D. Anderson Cancer Center with mastectomy and irradiation and without adjuvant chemotherapy. Patients with inflammatory carcinoma or synchronous bilateral primary tumors were excluded. There were 202 patients with Stage IIIA disease and 174 patients with Stage IIIB disease (AJC Staging--1983). In 124 patients the surgical management was confined to the breast only--total mastectomy (BR) and in 252 dissection of the axilla was performed--extended total, modified radical, or classic radical mastectomy (BR + AX). All patients had postoperative irradiation. The follow-up period ranged between 8 and 34 years. At 10 years, the actuarial disease-specific, relapse-free survival (DSRFS) rate for the entire group was 40%, and the actuarial locoregional control rate was 82%. For patients with Stage IIIA disease the DSRFS was 48% and locoregional control rate was 88%. For those with Stage IIIB disease, the figures were 30% and 74%, respectively. Most of the failures occurred within 5 years of the mastectomy and essentially all occurred within 10 years. When analyzed by type of surgery, both the locoregional control and DSRFS rates were improved by the axillary dissection, the difference being largely caused by fewer axillary node recurrences after dissection of both the breast and axilla than after removal of the breast alone. In the 252 patients in whom the axilla was assessed, the number of positive nodes was a powerful predictor of both locoregional control and survival. The DSRFS rates at 10 years for patients with 0, 1-3, and greater than or equal to 4 positive nodes were 63%, 48%, and 30%, respectively. The actuarial locoregional control rates at 10 years exceeded 95% for patients with 0-3 positive nodes and 75% for those with greater than or equal to 4 nodes. These results show that locoregionally advanced breast cancer is not a uniformly fatal disease when treated without chemotherapy and provide a baseline upon which to assess the value of adjuvant systemic therapy for this stage of disease.     

Survival after lumpectomy and mastectomy for early stage invasive breast cancer

BACKGROUND:

Randomized clinical trials (RCT) have demonstrated equivalent survival for breast‐conserving therapy with radiation (BCT) and mastectomy for early‐stage breast cancer. A large, population‐based series of women who underwent BCT or mastectomy was studied to observe whether outcomes of RCT were achieved in the general population, and whether survival differed by surgery type when stratified by age and hormone receptor (HR) status.

METHODS:

Information was obtained regarding all women diagnosed in the state of California with stage I or II breast cancer between 1990 and 2004, who were treated with either BCT or mastectomy and followed for vital status through December 2009. Cox proportional hazards modeling was used to compare overall survival (OS) and disease‐specific survival (DSS) between BCT and mastectomy groups. Analyses were stratified by age group (< 50 years and ≥ 50 years) and tumor HR status.

RESULTS:

A total of 112,154 women fulfilled eligibility criteria. Women undergoing BCT had improved OS and DSS compared with women with mastectomy (adjusted hazard ratio for OS entire cohort = 0.81, 95% confidence interval [CI] = 0.80‐0.83). The DSS benefit with BCT compared with mastectomy was greater among women age ≥ 50 with HR‐positive disease (hazard ratio = 0.86, 95% CI = 0.82‐0.91) than among women age < 50 with HR‐negative disease (hazard ratio = 0.88, 95% CI = 0.79‐0.98); however, this trend was seen among all subgroups analyzed.

CONCLUSIONS:

Among patients with early stage breast cancer, BCT was associated with improved DSS. These data provide confidence that BCT remains an effective alternative to mastectomy for early stage disease regardless of age or HR status. Cancer 2013. © 2012 American Cancer Society.     

Adjuvant chemotherapy and radiotherapy in triple-negative breast carcinoma: A prospective randomized controlled multi-center trial

Background and purpose: Triple-negative breast cancer (TNBC) presents a high risk breast cancer that lacks the benefit from hormone treatment, chemotherapy is the main strategy even though it exists in poor prognosis. Use of adjuvant radiation therapy, which significantly decreases breast cancer mortality, has not been well described among poor TNBC women. The aim of this study was to evaluate whether the combination of chemotherapy and radiotherapy could significantly increase survival outcomes in TNBC women after mastectomy. Patients and methods: A prospective randomized controlled multi-center study was performed between February 2001 and February 2006 and comprised 681 women with triple-negative stage I–II breast cancer received mastectomy, of them, 315 cases received systemic chemotherapy alone, 366 patients received radiation after the course of chemotherapy. Recurrence-free survival (RFS) and overall survival (OS) were estimated. Simultaneously local and systemic toxicity were observed. Results: After a median follow-up of 86.5 months, five-year RFS rates were 88.3% and 74.6% for adjuvant chemotherapy plus radiation and adjuvant chemotherapy alone, respectively, with significant difference between the two groups (HR 0.77 [95% CI 0.72, 0.98]; P = 0.02). Five-year OS significantly improved in adjuvant chemotherapy plus radiation group compared with chemotherapy alone (90.4% and 78.7%) (HR 0.79 [95% CI 0.74, 0.97]; P = 0.03). No severe toxicity was reported. Conclusions: Patients received standard adjuvant chemotherapy plus radiation therapy was more effective than chemotherapy alone in women with triple-negative early-stage breast cancer after mastectomy.     

Survival in stage I–III breast cancer patients by surgical treatment in a publicly funded health care system

BackgroundRecent investigations of breast cancer survival in the United States suggest that patients who receive mastectomy have poorer survival than those who receive breast-conserving surgery (BCS) plus radiotherapy, despite clinically established equivalence. This study investigates breast cancer survival in the publicly funded health care system present in Alberta, Canada.Patients and methodsSurgically treated stage I–III breast cancer cases diagnosed in Alberta from 2002 to 2010 were included. Demographic, treatment and mortality information were collected from the Alberta Cancer Registry. Unadjusted overall and breast cancer-specific mortality was assessed using Kaplan–Meier and cumulative incidence curves, respectively. Cox proportional hazards models were used to calculate stage-specific mortality hazard estimates associated with surgical treatment received.ResultsA total of 14 939 cases of breast cancer (14 633 patients) were included in this study. The unadjusted 5-year all-cause survival probabilities for patients treated with BCS plus radiotherapy, mastectomy, and BCS alone were 94% (95% CI 93% to 95%), 83% (95% CI 82% to 84%) and 74% (95% CI 70% to 78%), respectively. Stage II and III patients who received mastectomy had a higher all-cause (stage II HR = 1.36, 95% CI 1.13–1.48; stage III HR = 1.74, 95% CI 1.24–2.45) and breast cancer-specific (stage II HR = 1.39, 95% CI 1.09–1.76; stage III HR = 1.79, 95% CI 1.21–2.65) mortality hazard compared with those who received BCS plus radiotherapy, adjusting for patient and clinical characteristics. BCS alone was consistently associated with poor survival.ConclusionsStage II and III breast cancer patients diagnosed in Alberta, Canada, who received mastectomy had a significantly higher all-cause and breast cancer-specific mortality hazard compared with those who received BCS plus radiotherapy. We suggest greater efforts toward educating and encouraging patients to receive BCS plus radiotherapy rather than mastectomy when it is medically feasible and appropriate.     

Risk of second malignancy after Hodgkin's disease in a collaborative British cohort: the relation to age at treatment.

PURPOSE: To assess long-term site-specific risks of second malignancy after Hodgkin's disease in relation to age at treatment and other factors. PATIENTS AND METHODS: A cohort of 5,519 British patients with Hodgkin's disease treated during 1963 through 1993 was assembled and followed-up for second malignancy and mortality. Follow-up was 97% complete. RESULTS: Three hundred twenty-two second malignancies occurred. Relative risks of gastrointestinal, lung, breast, and bone and soft tissue cancers, and of leukemia, increased significantly with younger age at first treatment. Absolute excess risks and cumulative risks of solid cancers and leukemia, however, were greater at older ages than at younger ages. Gastrointestinal cancer risk was greatest after mixed-modality treatment (relative risk [RR] = 3.3; 95% confidence interval [CI], 2.1 to 4.8); lung cancer risks were significantly increased after chemotherapy (RR = 3. 3; 95% CI, 2.4 to 4.7), mixed-modality treatment (RR = 4.3; 95% CI, 2.9 to 6.2), and radiotherapy (RR = 2.9; 95% CI, 1.9 to 4.1); breast cancer risk was increased only after radiotherapy without chemotherapy (RR = 2.5; 95% CI, 1.4 to 4.0); and leukemia risk was significantly increased after chemotherapy (RR = 31.6; 95% CI, 19.7 to 47.6) and mixed-modality treatment (RR = 38.1; 95% CI, 24.6 to 55. 9). These risks were generally greater after treatment at younger ages: for patients treated at ages younger than 25 years, there were RRs of 18.7 (95% CI, 5.8 to 43.5) for gastrointestinal cancer after mixed-modality treatment, 14.4 (95% CI, 5.7 to 29.3) for breast cancer after radiotherapy, and 85.2 (95% CI, 45.3 to 145.7) for leukemia after chemotherapy (with or without radiotherapy). CONCLUSION: Age at treatment has a major effect on risk of second malignancy after Hodgkin's disease. Although absolute excess risks are greater for older patients, RRs of several important malignancies are much greater for patients who are treated when young. The increased risk of gastrointestinal cancers may relate particularly to mixed-modality treatment, and that of lung cancer to chemotherapy as well as radiotherapy; there are also well-known increased risks of breast cancer from radiotherapy and leukemia from chemotherapy. The roles of specific chemotherapeutic agents in the etiology of solid cancers after Hodgkin's disease require detailed investigation.     

Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers.

PURPOSE: To estimate the risk of contralateral breast cancer in BRCA1 and BRCA2 carriers after diagnosis and to determine which factors are predictive of the risk of a second primary breast cancer. PATIENTS AND METHODS: Patients included 491 women with stage I or stage II breast cancer, for whom a BRCA1 or BRCA2 mutation had been identified in the family. Patients were followed from the initial diagnosis of cancer until contralateral mastectomy, contralateral breast cancer, death, or last follow-up. RESULTS: The actuarial risk of contralateral breast cancer was 29.5% at 10 years. Factors that were predictive of a reduced risk were the presence of a BRCA2 mutation (v BRCA1 mutation; hazard ratio [HR], 0.73; 95% CI, 0.47 to 1.15); age 50 years or older at first diagnosis (v 相似文献   

早期乳腺癌的外科治疗策略

目的分析早期乳腺癌的外科治疗方式,探讨早期乳腺癌的外科治疗策略。方法收集2173例早期乳腺癌患者的临床资料,分析不同手术方式的适应证和禁忌证,比较不同手术的治疗效果和美容效果。结果全部患者的中位年龄为51岁(18～91岁)。未绝经患者1155例(53.2%)。0～Ⅰ期患者547例,Ⅱ期患者1626例。行根治性全乳切除1817例(83.6%),保乳手术229例(10.5%),术后一期再造55例(2.5%)。年轻和来停经患者、0～Ⅰ期患者和非浸润性癌患可选择保乳或再造;病理类型对选择保乳还是再造有影响(P=0.004)。全组中位随访14个月(3～64个月),保乳和全乳切除的无复发生存率(P=0.2435)、无病生存率(P=0.1395)和总生存率(P=0.9406)的差异无统计学意义。一期再造也未带来负面影响,随访期内1例复发,1例转移。保乳手术美容效果优良度为90.0%;乳房再造美容效果可接受度94.5%。结论有保乳意愿者,排除绝对禁忌并解决相对禁忌后方可保乳,保乳手术能同时满足治疗和美容目的。不适合保乳者,全乳切除后可行一期再造,能重塑乳房外形且不影响预后。在选择秩序上,保乳应先行考虑。将改良根治术、保乳手术和乳房再造有机统一,合理选择,更利于早期乳腺癌患者生理和心理的双重治疗。     

Paget disease of the breast: changing patterns of incidence, clinical presentation, and treatment in the U.S

BACKGROUND: Paget disease is an uncommon presentation of breast cancer that increased in incidence in the U.S. between 1973 and 1987. Characterized by malignant crusting or ulceration of the nipple, Paget disease can present in 1 of 3 ways: 1) in conjunction with an underlying invasive cancer, 2) in conjunction with underlying ductal carcinoma in situ (DCIS), or 3) alone without any underlying invasive breast carcinoma or DCIS. Paget disease can be treated with breast conservation by undergoing central lumpectomy. The objective of this study was to determine how the incidence, presentation, biomarkers, operative approach, and outcome of Paget disease have evolved in the U.S. since 1988. METHODS: Between 1988 and 2002, 1738 women who were diagnosed with Paget disease were reported in the 9 registries of the Surveillance, Epidemiology, and End Results Program. To the authors' knowledge, the current study on tumor characteristics, surgical intervention, and survival represented the largest series of Paget disease ever reported. RESULTS: Although the overall incidence of breast cancer increased between 1988 and 2002, the incidence of Paget disease concomitantly decreased by 45% (95% confidence interval, from -35% to -53%). This decreasing incidence was greatest for Paget disease associated with invasive cancer or DCIS. Invasive cancer associated with Paget disease more commonly was estrogen receptor negative, progesterone receptor negative, and of high histologic grade. Even when 60% of the disease was located centrally, only 293 of 1642 patients with Paget disease (18%) who were treated surgically underwent central lumpectomy. Patients with Paget disease who underwent breast conservation had outcomes equivalent to the outcomes among patients who underwent mastectomy. CONCLUSIONS: The incidence of Paget disease associated with underlying invasive cancer or DCIS decreased since 1988. Patients who underwent central lumpectomy and patients who underwent mastectomy for Paget disease had similar outcomes; nonetheless, most patients who were candidates for preservation underwent mastectomy.     

Locally advanced non inflammatory breast cancer treated by combined chemotherapy and preoperative irradiation: updated results in a series of 120 patients]

PURPOSE: To evaluate our updated data concerning survival and locoregional control in a study of locally advanced non inflammatory breast cancer after primary chemotherapy followed by external preoperative irradiation. PATIENTS AND METHODS: Between 1982 and 1998, 120 patients (75 stage IIIA, 41 stage IIIB, and 4 stage IIIC according to AJCC staging system 2002) were consecutively treated by four courses of induction chemotherapy with anthracycline-containing combinations followed by preoperative irradiation (45 Gy to the breast and nodal areas) and a fifth course of chemotherapy. Three different locoregional approaches were proposed, depending on tumour characteristics and tumour response. After completion of local therapy, all patients received a sixth course of chemotherapy and a maintenance adjuvant chemotherapy regimen without anthracycline. The median follow-up from the beginning of treatment was 140 months. RESULTS: Mastectomy and axillary dissection were performed in 49 patients (with residual tumour larger than 3 cm in diameter or located behind the nipple or with bifocal tumour), and conservative treatment in 71 patients (39 achieved clinical complete response or partial response >90% and received additional radiation boost to initial tumour bed; 32 had residual mass or=6 cm in diameter, p =0.002). Ten-year overall metastatic disease-free survival rate was 61%. After multivariate analysis, metastatic disease-free survival rates were significantly influenced by clinical stage (stage IIIA-B vs. IIIC, p =0.0003), N-stage (N0 vs. N1-2a, and 3c, p =0.017), initial tumour size (<6 vs. >or=6 cm in diameter, p =0.008), and tumour response after induction chemotherapy and preoperative irradiation (clinically complete response + partial response vs. non-response, p =0.0015). In the non conservative breast treatment group, of the 32 patients with no change in clinical tumour size after induction chemotherapy, the 10-year metastatic disease-free survival rate was 59% with only one local relapse. Arm lymphedema was noted in 17% (14 of 81) following axillary dissection and in 2.5% (1 of 39) without axillary dissection. Cosmetic results were satisfactory in 70% of patients treated by irradiation alone and in 51.5% of patients after wide excision and irradiation. CONCLUSION: Despite the poor prognosis of patients with locally advanced non inflammatory breast cancer resistant to primary anthracycline-based regimen, aggressive locoregional management using preoperative irradiation and mastectomy with axillary dissection offers a possibility of long term survival with low local failure rate for patients without extensive nodal disease. On the other hand, the rate of local failure seems to be high in patients with clinical partial tumour response following induction chemotherapy and breast-conserving treatment combining preoperative irradiation and large wide excision.     

Second malignant neoplasms after treatment for Hodgkin's disease in childhood or adolescence.

PURPOSE: To determine the frequency of and risk factors for second malignant neoplasms (SMNs) after treatment for Hodgkin's disease diagnosed in children and adolescents. PATIENTS AND METHODS: One hundred eighty-two consecutive, previously untreated patients with Hodgkin's disease who were younger than 20 years of age at diagnosis and who were referred to Roswell Park Cancer Institute (Buffalo, NY) for treatment between January 1, 1960, and December 31, 1989, were studied. Sex-specific standardized incidence ratios (SIRs) were calculated. Kaplan-Meier survival estimates and Cox regression analyses were performed to determine the relationship of several demographic and treatment variables to SMN incidence. RESULTS: Twenty-eight patients developed an SMN at a mean of 14.93 +/- 8.09 years (range, 2.65 to 29.88 years) after diagnosis of Hodgkin's disease. The cumulative percentage of patients who developed an SMN was 26.27 +/- 6.75% at 30 years after diagnosis. The SIR was 9.39 (95% confidence interval [CI], 4.05 to 18.49) for male patients and 10.16 (95% CI, 5.56 to 17.05) for female patients. The most frequent SMNs were thyroid cancer, breast cancer, nonmelanoma skin cancer, non-Hodgkin's lymphoma, and acute leukemia. Multivariate analysis of sex, treatment with any alkylating agent, treatment with doxorubicin, splenectomy, and relapse (as a time-dependent covariate) with time to SMN onset gave nonsignificant results. CONCLUSION: Successfully treated children and adolescents with Hodgkin's disease have a substantial risk for the occurrence of subsequent neoplasms. The most frequent SMNs (skin, thyroid, and breast) are readily detected by physical examination and available screening procedures.     

Repeat high-dose external beam irradiation for in-breast tumor recurrence after previous lumpectomy and whole breast irradiation

PURPOSE: To determine whether excision of an in-breast tumor recurrence (IBTR) plus 5000 cGy in 25 fractions to the new operative area is both tolerated and effective as treatment for an IBTR after previous lumpectomy and whole breast irradiation.METHODS AND MATERIALS: Thirty-nine women with an IBTR after lumpectomy and breast irradiation for invasive carcinoma (n = 31) or ductal carcinoma in situ (n = 8) were treated with excision of the IBTR and radiotherapy (RT), 5000 cGy in 25 fractions, to the operative area using electrons of appropriate energy. The interval from completion of the first course of RT to diagnosis of the IBTR ranged from 16 to 291 months (median 63).RESULTS: The repeat course of RT to the new operative area was well tolerated in all patients, and no late sequelae occurred other than skin pigmentation changes. Eight patients, including 2 with suspicious bone scans at the time of IBTR, developed distant metastases, and 7 died 21-71 months (median 48) after retreatment. One patient was alive with distant metastases at 27 months after retreatment. Four of the 8 patients who developed distant metastases also had a second IBTR, and 3 died with persistent disease in the breast. An additional 4 patients, for a total of 8, had a second IBTR. Three were alive and free of disease after mastectomy, and 1 was alive and free of disease after mastectomy and additional RT for chest wall recurrence. An additional patient developed recurrence in the axilla 9 months after reirradiation and was treated with surgery; she died free of disease at 63 months. One patient underwent mastectomy for suspected persistent disease 2 months after completion of repeat RT; no evidence of recurrent tumor was found in the removed breast. Thus, 30 women (76.9%) had an intact breast free of tumor at death or at last follow-up 1-180 months (median 51.5) after reirradiation. Using the Kaplan-Meier life table analysis, the estimated overall and disease-free 5-year survival rate for the 39 patients was 77.9% and 68.5%, respectively.CONCLUSION: For select patients with an IBTR after lumpectomy and breast irradiation, excision of the IBTR followed by repeat external beam RT to the operative area may be an acceptable alternative to mastectomy.