The impact of postmastectomy radiotherapy on local control in patients with invasive lobular breast cancer

Purpose

The aim of this population-based study was to examine the impact of postmastectomy radiotherapy on the risk of local recurrence in patients with invasive lobular breast cancer (ILC).

Methods

The population-based Eindhoven Cancer Registry was used to select all patients with ILC, who underwent mastectomy in five general hospitals in the southern part of the Netherlands between 1995 and 2002. Of the 499 patients 383 patients fulfilled the eligibility criteria. Of these patients, 170 (44.4%) had received postmastectomy radiotherapy. The median follow-up was 7.2 years. Fourteen patients (3.7%) were lost to follow-up.

Results

During follow-up 22 patients developed a local recurrence, of whom 4 had received postmastectomy radiotherapy. The 5-year actuarial risk of local recurrence was 2.1% for the patients with and 8.7% for the patients without postmastectomy radiotherapy. After adjustment for age at diagnosis, tumour stage and adjuvant systemic treatment, the patients who underwent postmastectomy radiotherapy were found to have a more than 3 times lower risk of local recurrence compared to the patients without (Hazard Ratio 0.30; 95% Confidence Interval: 0.10-0.89).

Conclusion

Local control is excellent for patients with ILC who undergo postmastectomy radiotherapy and significantly better than for patients not receiving radiotherapy.     

乳腺癌保留乳房手术后的放射治疗技术

放射治疗是早期乳腺癌保乳治疗的一个不可缺少的部分。荟萃分析显示：保乳术后放射治疗可以降低同侧乳腺肿瘤的复发率和患者的癌症病死率,放射治疗和未放射治疗患者的5年同侧乳腺局部复发率分别为79／6和26％,15年乳腺癌病死率分别为30．5％和35．9％。目前早期乳腺癌保乳术后放射治疗主要包括全乳房照射50．0Gy（每次2．0Gy）,然后瘤床补量照射10．O～16．0Gy。     

Premenopausal breast cancer patients treated with conservative surgery, radiotherapy and adjuvant chemotherapy have a low risk of local failure

The use of adjuvant chemotherapy in premenopausal breast cancer patients with positive nodes is now routine, but the optimal local treatment of these patients is uncertain. To determine the effect of adjuvant chemotherapy on the likelihood of local recurrence as the first site of failure in premenopausal patients treated with conservative surgery (CS) and radiotherapy (RT), we examined the outcome of 74 patients treated with CS, RT, and adjuvant chemotherapy and compared it to the outcome in 192 patients treated with CS and RT alone. Adjuvant chemotherapy consisted of four or more cycles of either a doxorubicin-containing regimen or cyclophosphamide, methotrexate, and 5-fluorouracil. All patients were less than 50 years old, had UICC-AJCC Stage I or II breast cancer treated between 1968 and 1981, had gross excision of the primary tumor, and had a total radiation dose to the primary tumor bed of greater than or equal to 6000 cGy. Factors predicting for local recurrence, such as extensive intraductal carcinoma and age less than 35, were equivalent in the two groups. Women treated with adjuvant chemotherapy had significantly worse T- and N-stages than women treated with conservative surgery and radiotherapy alone: 61% versus 36% had T2 tumors (p = 0.0003), 34% versus 6% had clinically positive nodes (p less than 0.0001), and 97% versus 4% had pathologically positive nodes (p less than 0.0001). Despite the poorer prognosis of patients treated with adjuvant chemotherapy, within 5 years of diagnosis, 4% of patients who received adjuvant chemotherapy had their initial relapse in the breast and 24% had initial failure elsewhere, compared with 15% local failure first and 14% failure elsewhere first for those treated without chemotherapy (p = 0.01). We conclude that premenopausal patients with positive nodes treated with combined modality therapy (conservative surgery, radiation therapy, and adjuvant chemotherapy) have a low risk of local recurrence as a first site of failure. These results suggest a possible interaction between radiation therapy and chemotherapy in their effects on local tumor control.     

The 10-Year Local Recurrence and Partial Breast Radiotherapy for Early Breast Cancer Treated by Conservative Surgery

C onservative surgery for early breast cancer was proposed by Keynes in 1924 and has been one of the main therapeutic mea- sures. It has been confirmed by abundant literature that the efficacy of conservative surgery plus whole breast radiotherapy is the …     

Long-term prognosis of patients with local recurrence after conservative surgery and radiotherapy for early breast cancer

We have studied the long-term prognosis of 266 patients considered to have isolated local recurrence in the breast following conservative surgery and radiotherapy for early breast cancer. The median follow-up of the patients still alive after diagnosis of local relapse was 11.2 years. At 10 years from the date of salvage treatment, the overall survival rate for the 226 patients with invasive local recurrence was 39% (95% CI, 32-46), the distant recurrence-free survival rate was 36% (95% CI, 29-42), and the local control rate (i.e., survival without subsequent local recurrence or local progression) was 68% (95% CI, 62-75). Among patients with a local recurrence at or near the original tumour site a better distant disease-free survival was observed for patients with recurrences measuring 1cm or less, compared to those with larger recurrences. This suggests, though does not prove, that early detection of local recurrence can improve the treatment outcome but might as well point towards a different biologic behaviour, facilitating early detection.     

早期乳腺癌保乳术后局部复发与术后放疗可行性的分析

目的总结早期乳腺癌保乳手术后局部复发的表现,分析全乳放疗的作用。方法保乳治疗原发性早期乳腺癌134例,其中0期1例,Ⅰ期78例,Ⅱa期55例。行象限切除加腋窝淋巴结清扫术125例,单纯肿块局部广泛切除术9例。术后全乳切线加瘸床放疗102例,全乳切线照射整个乳房,6 MV X线,为减少肺受照量,采用半开野等中心照射,中平面剂量45 Gy,瘤床补加电子束剂量15 Gy。其余32例未行全乳放疗。视术后淋巴结状况行区域淋巴引流区照射。结果随访5～15年,失访5例。术后5年局部复发率、远处转移率、生存率分别为3．7%、2．2%、95．5%。复发共5例,均为浸润性癌,术后病理证实区域淋巴结均为阴性。保乳术后不加全乳放疗组局部复发率似有所提高（9．4%∶2．0%）,但差异无统计学意义,可能与病例数少有关。局部复发病例中原位复发4例。结论结论保乳术后放疗是必要的。局部复发的主要形式是原位复发。足够剂量的只限于肿瘤邻近区域的放疗方式应该是可行的。     

Effect of tumor infiltrating lymphocyte on local control of rectal cancer after preoperative radiotherapy

Objective： To study the effect of tumor infiltrating lymphocytes at cancer nest on local control of rectal cancer after preoperative radiotherapy. Methods： From Jan. 1999 to Oct. 2007, a total of 107 patients with rectal cancer were reviewed. They were treated by preoperative radiotherapy, 30 Gy/10 fractions/12 days. Two weeks later, the patient underwent a surgical operation. Their pathological samples were kept in our hospital before and after radiotherapy. Lymphocyte infiltration （LI） degree, pathologic degradation and fibrosis degree after radiotherapy in paraffin section were evaluated under microscope. Results： After followed-up of 21 months （2-86 months）, a total of 107 patients were reviewed. Univariate analysis showed that lymphocyte infiltration （LI）, fibrosis and pathologic changes after radiotherapy were significant factors on local control. Logistic regression analysis showed that LI after radiotherapy was a significant effect factor on local control. Conclusion： LI, fibrosis and pathologic degradation after radiotherapy are significant for local control of rectal cancer after preoperative radiotherapy. LI after radiotherapy was a significantly prognostic index for local control of rectal cancer after preoperative radiotherapy.     

The impact of age on local control in women with pT1 breast cancer treated with conservative surgery and radiation therapy

The aim of the study was to evaluate the importance of young age with regard to local control in a prospective cohort of 1085 women with pathological T1 tumours treated with breast conservative treatment (BCT). Patients were divided into two age groups: 40 years or younger, 7.8%, and older than 40 years, 92.2%. With a median follow-up of 71 months, the local recurrence rate was 10.6% in women < or =40 years, and 3.7% in older women. The local recurrence-free survival (LRFS) was significantly different for the two age groups, respectively 89%, < or =40 years, and 97.6%, >40 years (P=0.0046). A separate analysis showed a significantly decreased LRFS for young women with a positive family history, 75.4% versus 98.4% 5-year LRFS for older women. A worse LRFS for young women with a negative lymph node status was also observed, respectively 84% versus 98% 5-year LRFS (both P<0.001). In a multivariate analysis, taking into account the pre-treatment and treatment factors, age < or =40 years, was the only significant predictor of a decreased LRFS. Thus, young age is an important factor in relation to local control. In a subset analysis, this significant adverse effect of young age on outcome appears to be limited to the node-negative patients and those with a positive family history. To date, there is no evidence that young women with pT1 breast cancer, treated by mastectomy have an improved outcome when compared with those treated with conservative surgery and radiotherapy. Taking into account results from a subset analysis suggests that giving systemic therapy to a subgroup of women who are < or =40 years, node-negative and/or have a positive family history might give a better local control.     

The relation between the presence and extent of lobular carcinoma in situ and the risk of local recurrence for patients with infiltrating carcinoma of the breast treated with conservative surgery and radiation therapy

BACKGROUND: When found in an otherwise benign biopsy, lobular carcinoma in situ (LCIS) has been associated with an increased risk of development of a subsequent invasive breast carcinoma. However, the association between LCIS and the risk of subsequent local recurrence in patients with infiltrating carcinoma treated with conservative surgery and radiation therapy has received relatively little attention. METHODS: Between 1968 and 1986, 1625 patients with clinical Stage I-II invasive breast carcinoma were treated at the Joint Center for Radiation Therapy at Harvard Medical School with breast-conserving surgery (CS) and radiation therapy (RT) to a total dose to the primary site of > or =60 grays. Analysis was limited to 1181 patients with infiltrating ductal carcinoma, infiltrating lobular carcinoma, or infiltrating carcinoma with mixed ductal and lobular features who, on review of their histologic slides, had sufficient normal tissue adjacent to the tumor to evaluate for the presence of LCIS and also had a minimum potential follow-up time of 8 years. The median follow-up time was 161 months. RESULTS: One hundred thirty-seven patients (12%) had LCIS either within the tumor or in the macroscopically normal adjacent tissue. The 8-year crude risk of recurrence was not significantly increased for patients with LCIS associated with invasive ductal, invasive lobular, or mixed ductal and lobular carcinoma. Among the 119 patients with associated LCIS adjacent to the tumor, the 8-year rate of local recurrence was 13%, compared with 12% for the 1062 patients without associated LCIS. For the 70 patients with moderate or marked LCIS adjacent to the tumor, the 8-year rate of local recurrence was 13%. The extent of LCIS did not affect the risk of recurrence. The risks of contralateral disease and of distant failure were similarly not affected by the presence or extent of LCIS. CONCLUSIONS: Breast-conserving therapy involving limited surgery and radiation therapy is an appropriate method of treating patients with invasive breast carcinoma with or without associated LCIS. Neither the presence nor the extent of LCIS should influence management decisions regarding patients with invasive breast carcinoma. [See editorial counterpoint and reply to counterpoint on pages 978-81 and 982-3, this issue.] Copyright 2000 American Cancer Society.     

Radiation pneumonitis in breast cancer patients treated with conservative surgery and radiation therapy

The likelihood of radiation pneumonitis and factors associated with its development in breast cancer patients treated with conservative surgery and radiation therapy have not been well established. To assess these, we retrospectively reviewed 1624 patients treated between 1968 and 1985. Median follow-up for patients without local or distant failure was 77 months. Patients were treated with either tangential fields alone (n = 508) or tangents with a third field to the supraclavicular (SC) or SC-axillary (AX) region (n = 1116). Lung volume treated in the tangential fields was generally limited by keeping the perpendicular distance (demagnified) at the isocenter from the deep field edges to the posterior chest wall (CLD) to 3 cm or less. Seventeen patients with radiation pneumonitis were identified (1.0%). Radiation pneumonitis was diagnosed when patients presented with cough (15/17, 88%), fever (9/17, 53%), and/or dyspnea (6/17, 35%) and radiographic changes (17/17) following completion of RT. Radiographic infiltrates corresponded to treatment portals in all patients, and in 12 of the 17 patients, returned to baseline within 1-12 months. Five patients had permanent scarring on chest X ray. No patient had late or persistent pulmonary symptoms. The incidence of radiation pneumonitis was correlated with the combined use of chemotherapy (CT) and a third field. Three percent (11/328) of patients treated with a 3-field technique who received chemotherapy developed radiation pneumonitis compared to 0.5% (6 of 1296) for all other patients (p = 0.0001). When patients treated with a 3-field technique received chemotherapy concurrently with radiation therapy, the incidence of radiation pneumonitis was 8.8% (8/92) compared with 1.3% (3/236) for those who received sequential chemotherapy and radiation therapy (p = 0.002). A case:control analysis was performed to determine if the volume of lung irradiated (as determined using central lung distance [CLD]) was related to the risk of developing radiation pneumonitis. Three control patients were matched to each case of radiation pneumonitis based on age, side of lesion, chemotherapy (including sequencing), use of a third field, and year treated. Lung volumes were similar in the radiation pneumonitis cases and controls. We conclude that radiation pneumonitis following conservative surgery and radiation therapy for breast cancer is a rare complication, and that it is more likely to occur in patients treated with both a 3-field technique and chemotherapy (particularly given concurrently with radiation therapy). Over the limited range of volumes treated, lung volume was not associated with an increased risk of radiation pneumonitis.     

Time-course of local recurrence following conservative surgery and radiotherapy for early stage breast cancer

The time-course of local failure following conservative surgery and radiotherapy (S+RT) for early breast cancer is not well established. We therefore examined the time-course and patterns of breast recurrence as a first site of treatment failure in a group of 607 AJCC clinical Stage I or II invasive breast carcinomas treated from 1968-81. Sixty-seven patients had a breast failure (11%), corresponding to 5- and 10-year actuarial rates of 10% and 16%. The hazard rate (i.e., the risk per unit time of a failure) for any breast failure increased over the first 2 years, was fairly constant at about 2.5%/year over the period from 2 to 6 years after treatment, and then decreased to about 1%/year at 8 years. The majority of failures were at or near the primary tumor site (33 true recurrences (TR) and 15 marginal misses (MM). In addition there were 12 failures at sites at least several cm from the boosted volume (E), 6 recurrences in the skin without a parenchymal mass (S), and 1 patient with an unclassifiable failure. Recurrences at or near the primary site (TR/MM) occurred earlier (median 38.5 mo, range 12-87 mo) than recurrences at distant sites in the breast (E) (median 64.5 mo, range 26-90). The hazard rate for TR/MM increased over the first 2-1/2 years to reach approximately 2%/year, remained at that level till about 5 years after treatment, and then decreased to about 0.5%/year at 8 years following RT. By contrast, the hazard rate for E increased slowly with time to approximately 1%/year at 5 years, with little change in the rate after that time. We conclude that the time-course of the development of local recurrence after S+RT is protracted. The majority of failures appear at or near the primary tumor site; these are seen mainly in the first 7 years following RT. Recurrences at distant sites in the breast have an even more protracted time-course. Such recurrences are rare in the first 4 years following RT. Our results emphasize the need to obtain long follow-up in these patients, both to detect these recurrences promptly and to properly evaluate the results of S+RT.     

The effect of young age on tumor recurrence in the treated breast after conservative surgery and radiotherapy

Prognostic factors for local recurrence following conservative surgery and radiation therapy for patients with early breast cancer have not been fully established. To evaluate the importance of young age as a prognostic factor for local recurrence, we reviewed the results of treatment of 597 patients with 607 UICC-AJCC Stage I or II breast cancers, 47 of which were diagnosed when the patient was less than 35 years old. All were treated with excisional biopsy and a total dose to the site of the primary tumor of 60 Gy or more. The median follow-up in survivors was 63 months. Patient age and the presence of an extensive intraductal component (EIC) were both highly associated with the likelihood of tumor recurrence in the treated breast. Patients under 35 had an actuarial 5-year recurrence rate of 26%, compared to 10% for older patients (p = 0.002). Patients with an EIC had a breast recurrence rate of 25%, compared to 5% when EIC was absent (p less than 0.0001). Although the incidence of an EIC was higher in the younger subgroup (44% vs. 31%), this alone did not account for the difference in in breast recurrence rates, since younger patients had a higher recurrence rate than older patients even when an EIC was absent (22% vs. 3%, p = 0.0003). We conclude that the age of the patient is an important prognostic factor for local recurrence following conservative surgery and radiation therapy. This finding is in part attributed to the observation that younger women are more likely to have tumors with an EIC than older women, but even when an EIC is absent, they may be at an increased risk of local recurrence. However, caution is required in interpreting these findings with regard to selecting among treatment options until further data are available comparing the results of conservative surgery and radiation therapy to those of mastectomy in younger patients.     

乳腺癌保乳术后同步加量调强放疗的临床疗效

目的:探讨乳腺癌保乳术后同步加量调强放疗的疗效、不良反应及美容效果。方法:2008年~2010年收治乳腺癌保乳术后患者78例,其中38例行瘤床同步加量调强放疗（A组）,剂量分割方案为全乳50Gy/25次（2Gy/次）,瘤床同步加量至60Gy/25次（2.4Gy/次）,总疗程33~35天;40例行常规分割调强放疗（B组）,剂量分割方案为全乳50Gy/25次,后续瘤床推量10Gy/5次（2Gy/次）,总疗程40~42天。应用Kaplan-Meier法生存分析,Log-rank法检验差异。结果:中位随访时间为73个月,随访率为100%。两组5年总生存率均为100%。A组和B组5年局部无复发生存率、无病生存率分别为97.4%、97.5%（P=0.978）;97.4%、95.0%（P=0.589)。A组和B组1、2级急性皮肤反应发生率分别为57.9%、52.5%(P＝0.632); 13.2%、12.5%(P＝0.931);A组和B组的1级皮肤及皮下组织晚期反应发生率分别为15.8%、15.0%（P=0.932）;1级白细胞减少发生率分别为7.9%、10.0%（P=0.745）。A组和B组在放疗前、放疗后3、5年美容效果优良率分别为86.8%、87.5%（P=0.931）;84.2%、85.0%（P=0.932）;81.6%、82.5%（P=0.916）。结论:保乳术后同步加量调强放疗的疗效与常规分割调强放疗相似,美容效果及不良反应相当。     

Cerebral haemangiopericytoma treated with conservative surgery and radiotherapy

Cerebral haemangiopericytomas are rare tumours that resemble meningiomas but behave more aggressively, with a tendency to metastasize. We report two patients with haemangiopericytoma who had limited surgical resections owing to perioperative blood loss but who had massive tumour shrinkage after a course of radical radiotherapy. We suggest a more conservative surgical approach to the management of these tumours.     

Influence of interfraction interval on local tumor control in patients with limited-disease small-cell lung cancer treated with radiochemotherapy

PURPOSE: To investigate the influence of interfraction interval (IFI) on local recurrence-free survival (LRFS) in patients with limited-disease small-cell lung cancer (LD SCLC) treated with accelerated hyperfractionated radiotherapy (Acc Hfx RT) and concurrent cisplatin and etoposide (PE). METHODS AND MATERIALS: A total of 103 patients were treated with either "early" (Cycle 1) or "late" (Cycle 4) concurrent Acc Hfx RT/PE. Two daily fractions were nonrandomly given using an IFI of either 4.5-5.0 h ("shorter") (n = 52) or 5.5-6.0 h ("longer") (n = 51). RESULTS: The median LRFS and 5-year LRFS rate for all 103 patients were 52 months and 48%, respectively. Besides gender, Karnofsky performance status, and treatment group, IFI also influenced LRFS, whereas age and weight loss did not. When a multivariate model was used, IFI was marginally insignificant (p = 0.0770) as a predictor of LRFS. In terms of individual treatment groups, IFI was not significant in "early" Acc Hfx RT/PE but showed a strong trend in a "late" Acc Hfx RT/PE regimen. Although a shorter IFI led to a higher incidence of high-grade (>or=3) esophagitis, leukopenia, and infection, a correlation analysis of toxicities with all potential prognostic factors showed that a shorter IFI was not an independent predictor of any acute high-grade toxicity. CONCLUSION: "Shorter" IFI had a marginally insignificant influence on LRFS. A strong trend favoring it was observed in patients treated with "late" concurrent Acc Hfx RT/PE. This may be of interest because it could contribute to further understanding of potential biologic parameters influencing treatment outcome.     

乳腺癌保乳术后同步加量IMRT前瞻性研究

目的 前瞻性评估乳腺癌保乳术后瘤床同步加量IMRT的疗效和不良反应。     

Influence of the delay between conservative surgery and radiation therapy on local relapse in node-positive breast tumor

It has been shown that a delay in radiotherapy (RT) initiation resulted in a higher local relapse (LR) rate. The present analysis investigated retrospectively if the RT-adjuvant therapy sequence modified local-disease-free survival (L-DFS) after breast-conserving surgery (BCS) in node-positive (N +) breast cancer patients. Among seven French Adjuvant Study Group trials, 1,831 patients were assessable: 475 received RT directly after BCS, 567 after the 3rd chemotherapy (CT) cycle, and 789 after the 6th CT cycle. In the 1,356 patients receiving CT, it consisted of FEC regimens (fluorouracil, epirubicin, cyclophosphamide) in 83.5% of patients. After a 102-month median follow-up, 214 patients (11.7%) developed LR. The 9-year L-DFS rates were 92.0%, 81.5%, and 87.4%, respectively (p < 0.0001). In the multivariate analysis, the timing of RT was not associated with a higher rate of LR, whereas tumor size and hormonotherapy were prognostic factors. In our population, there was no increase in the risk of LR when RT was delayed to deliver adjuvant CT. Prognostic factors were tumor size, and hormonotherapy. The number of CT courses could modify this risk.     

Local failure is responsible for the decrease in survival for patients with breast cancer treated with conservative surgery and postoperative radiotherapy.

PURPOSE: The aim of the present study was to evaluate the role of local failure (LF) in the survival of patients treated with lumpectomy and postoperative radiotherapy and to investigate whether LF is not only a marker for distant metastasis (DM) but also a cause. METHODS: Charts of patients treated with breast conservative surgery between 1969 and 1991 were reviewed retrospectively. There were 2,030 patients available for analysis. The median duration of follow-up was 6 years. A Cox regression multivariate analysis was performed using LF as a time-dependent covariate. RESULTS: Local control (LC) was 87% at 10 years. Local failure led to poorer survival at 10 years than local control (55% v 75%, P < .00). In a Cox model, local failure was a powerful predictor of mortality. The relative risk associated with LF was 3.6 for mortality and 5.1 for DM (P < .00). In patients with LF, the rate of DM peaked at 5 to 6 years, whereas it peaked at 2 years for patients with LC. The mean time between surgery and DM was 1,050 days for patients without LF and 1,650 days for patients with LF (P < .00). CONCLUSION: Our results show that local failure is associated with an increase in mortality. The difference in the time distribution of distant metastasis for LF and LC could imply distinct mechanisms of dissemination. Local failure should be considered not only as a marker of occult circulating distant metastases but also as a source for new distant metastases and subsequent mortality.     

The impact of lobular histology on breast cancer treatment

Lobular neoplasias are a distinct clinical entity with subtle differences in locoregional treatment considerations when compared with ductal cancers. Although overall surgical recommendations do not differ significantly between breast cancers of lobular versus ductal histology, there are important distinctions that should be considered as part of patient care, particularly with respect to recommendations regarding management of the contralateral breast and genetic testing. Because the lobular subtype of breast cancer is underrepresented in studies of molecular prognostic markers, the results of such testing must be interpreted with caution until they are validated specifically in patients with lobular histology. Until then, the mainstay of sound treatment decision-making remains a thorough clinical understanding of the disease and of the factors that can have an impact on outcome.