A Systematic Overview of Radiation Therapy Effects in Breast Cancer

A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for breast cancer is based on data from 29 randomized trials, 6 meta-analyses and 5 retrospective studies. In total, 40 scientific articles are included, involving 41 204 patients. The results were compared with those of a similar overview from 1996 including 285 982 patients. The conclusions reached can be summarized as follows: There is strong evidence for a substantial reduction in locoregional recurrence rate following postmastectomy radiation therapy to the chest wall and the regional nodal areas.There is strong evidence that postmastectomy radiation therapy increases the disease-free survival rate.There are conflicting data regarding the impact of postmastectomy radiotherapy upon overall survival.There is strong evidence that breast cancer specific survival is improved by postmastectomy radiotherapy.There is strong evidence for a decrease in non-breast cancer specific survival after postmastectomy radiotherapy.There is some evidence that overall survival is increased by optimal postmastectomy radiation therapy.There is strong evidence that postmastectomy radiotherapy in addition to surgery and systemic therapy in mainly node-positive patients decreases local recurrence rate and improves survival.There is moderate evidence that the decrease in non-breast cancer specific survival is attributed to cardiovascular disease in irradiated patients.There are conflicting data whether breast conservation surgery plus radiotherapy is comparable to modified radical mastectomy alone in terms of local recurrence rate.There is strong evidence that breast conservation surgery plus radiotherapy is comparable to modified radical mastectomy alone in terms of disease-free survival and overall survival.There is strong evidence that postoperative radiotherapy to the breast following breast conservation surgery results in a statistically and clinically significant reduction of ipsilateral breast recurrences followed by diminished need for salvage mastectomies.There is strong evidence that the omission of postoperative radiotherapy to the breast following breast conservation surgery has no impact on overall survival. In one meta-analysis including three randomized studies a survival advantage is demonstrated by Bayesian statistics.There is strong evidence that the addition of a radiation boost after conventional radiotherapy to the tumour bed after breast conservation surgery significantly decreases the risk of ipsilateral breast recurrences but has no impact on overall survival after short follow-up.There is strong evidence for the use of postoperative radiotherapy to the breast following breast conservation surgery for DCIS (ductal breast cancer in situ). Radiotherapy leads to a clinically and statistically significant reduction of both non-invasive and invasive ipsilateral breast recurrences.There is insufficient evidence to define the optimal integration of systemic adjuvant therapy and postoperative radiotherapy.There are limited data on radiotherapy-related morbidity in breast cancer. No conclusions can be drawn.     

The role of postoperative radiotherapy in node negative breast cancer patients with pT3-T4 disease.

AIMS: To evaluate the role of postmastectomy radiotherapy (PMRT) in patients with pT3-T4N0M0 breast cancer. METHODS: 156 patients with T3-T4N0M0 breast cancer were retrospectively analyzed. RESULTS: Locoregional recurrences were seen in 17 of 156 patients with a median time for development of 27 months (5.7-248.7 months). Two of 9 patients who were not treated with post-operative radiation therapy had locoregional recurrence as compared with 16 of 147 patients receiving radiotherapy. In multivariate analysis, presence of locoregional recurrence was the only significant prognostic factor for overall survival (18% vs. 86%, p<0.001, RR=9.05). The patients with a median number of dissected lymph nodes >or=10 had a significantly better locoregional disease free survival rate as compared with patients with dissected lymph nodes <10 (90% vs. 78%, p=0.04). Chest wall recurrences were clearly higher in patients without chest wall RT since 5 of 49 patients without RT had recurrences in the chest wall region while only 4 of 107 who received chest wall RT had recurrence. However receiving RT to peripherical lymphatic regions had no additional effect on reducing recurrences in these regions (5% vs. 4%). CONCLUSIONS: Due to the lack of phase III randomized trials directly addressing the role of postmastectomy radiotherapy in these stages, our series suggest that postmastectomy radiotherapy to the ipsilateral chest wall is recommended for patients with PT3N0 and T4N0 breast cancer. The need for irradiating axillary or supraclavicular region shall be neglected in patients who undergo sufficient axillary sampling.     

Cardiac mortality and morbidity after breast cancer treatment.

BACKGROUND: Breast conservation treatment for early-stage breast cancer has been demonstrated to be equivalent to mastectomy in a large number of randomized trials. A number of earlier studies of surgery with or without radiation did not show an improvement in overall survival despite large reductions in local recurrence rates. Numerous randomized trials have demonstrated that postmastectomy radiation to the chest wall and regional nodes in high-risk early-stage patients provides improvements in local-regional control and overall survival. METHODS: This article reviews the medical literature pertaining to long-term cardiac toxicity in early-stage breast cancer patients treated with either breast conservation or postmastectomy radiation. RESULTS: A decrease in breast cancer deaths associated with postoperative irradiation was offset by an increase in cardiovascular deaths in early studies. Cardiac toxicity of breast irradiation is a late event, manifesting clinically 10 or more years after breast cancer treatment. The excess deaths were directly related to radiation techniques that exposed excessive volumes of the heart, leading to the development of new techniques designed to shield the heart and reduce the risk of cardiac toxicity. CONCLUSIONS: This review examines the original and contemporary studies of radiation for postmastectomy and breast conservation treatment for early-stage breast cancer, discusses the long-term cardiac mortality and morbidity data from these studies, and reviews the known risk factors associated with cardiac toxicity after irradiation for breast cancer.     

Radiotherapy for breast cancer: today and tomorrow

Breast conservation therapy (BCT) with lumpectomy and radiation has allowed many women to preserve their breasts and avoid disfiguring surgery. Lumpectomy and breast irradiation is a standard therapy for early breast cancer patients who desire breast conservation. However, the overall rate of mastectomy exceeds that of BCT in the United States. There have been significant advances in patient awareness of the options available for local management of early breast cancer and changes in the attitudes of physicians, including surgeons, allowing a gradual rise in the rate of BCT in the last two decades. Now, investigations are designed to define subgroups of patients with early breast cancer in whom radiation can be safely omitted. In locally advanced breast cancer, neoadjuvant chemotherapy has allowed some women to have BCT after initial cytoreduction. This approach results in excellent local control when patients are carefully selected for BCT. There is renewed interest in postmastectomy radiation for early breast cancer patients with 1 to 3 positive lymph nodes. In this intermediate risk group for locoregional recurrence, the addition of chest wall and regional lymphatic irradiation to adjuvant systemic therapy has potential for significant improvement in ultimate survival. This concept is novel in breast cancer, a disease that was believed to be systemic at inception and in which only systemic control was thought to impact survival. In this era of effective adjuvant systemic therapy for breast cancer, local control measures have become more important as local control has real potential for impacting survival.     

Radiation-Induced Ischemic Heart Disease in Breast Cancer: A Review

It is well established that adjuvant radiotherapy (RT) reduces loco-regional recurrences in breast cancer. The effect on overall survival, on the other hand, is a much-debated issue. Some old trials with a long follow-up as well as the first report on the overview of the randomized RT trials initiated before 1975 showed a reduced survival among irradiated patients compared with the surgical controls. In the update of the overview this proved to be due to cardiac deaths. In two more recent studies, adjuvant RT in the postmastectomy setting improved the survival of node-positive premenopausal patients who were also treated with chemotherapy. In one of these trials it was indicated that cardiac mortality was not increased. There are few data concerning the cardiac side effects of RT after conservative surgery. Some studies suggest that radiation-induced heart disease may be a potential problem also among these patients. Therefore, the search for both the causes of radiation-induced heart disease and preventive measures is crucial issues in breast cancer radiation oncology.     

Shoulder and arm problems after radiotherapy for primary breast cancer

There is little, if any, difference in disease-free or overall survival for patients with stage I and II breast cancer treated by either breast conservation therapy or mastectomy. With either treatment, there may be cosmetic and functional problems related to arm edema, limited shoulder motion, and shoulder pain. The extent to which factors such as surgery, radiotherapy, systemic therapy, and patient characteristics affect development of arm edema, limited shoulder motion, and shoulder pain is not well documented. We undertook a prospective study of arm edema, limited shoulder motion, and shoulder pain in every patient (N = 331) seen during a 6-month period for follow-up after radiotherapy postlumpectomy or mastectomy for primary breast cancer. Local treatment included lumpectomy and breast irradiation with (n = 232) or without (n = 97) axillary dissection. Ten other women underwent mastectomy and postoperative radiotherapy. Doses to each region treated were 50 Gy in 25 fractions. The operative area was treated with an additional 1,000 Gy in approximately 60% of patients. Twelve patients received axillary irradiation without axillary dissection, and 11 patients received supraclavicular irradiation. Chemotherapy with or without tamoxifen was used in 71 patients and tamoxifen alone was used in 150 patients. One hundred ten patients did not receive any adjuvant therapy. Ipsilateral arm edema occurred in 20 women (6.0%), limited ipsilateral shoulder motion in 5 (1.5%), and ipsilateral shoulder pain in 5 (1.5%). Edema was mild (1+) in 15 patients and moderate (2+) in five patients. Multivariate analysis revealed that the risk of arm edema was significantly increased in black women (p = 0.005, 4/18 versus 16/313 whites) and with mastectomy (p = 0.048, 2/10 versus 18/321 with lumpectomy). There is a low incidence of arm edema, decreased range of motion of the ipsilateral shoulder, and shoulder-arm pain in patients undergoing postlumpectomy or postmastectomy radiotherapy. The risk of arm edema is increased in black women and in patients after mastectomy as opposed to lumpectomy.     

Sophisticated radiotherapy with optimal surgery is the way forward

PURPOSE OF REVIEW: Radiotherapy has been one of the cornerstones of treatment for breast cancer for more than a century and has contributed to conservation of the breast and improved locoregional control after mastectomy. This review assesses the most recent evidence generated by clinical scientists in the field of radiotherapy for breast cancer. RECENT FINDINGS: Results from mature trials investigating the role of radiotherapy in breast cancer treatment and the publication of meta-analyses of treatment effects have shown that in addition to improvements in local control, a survival benefit is obtained in several disease settings. These include breast-conserving therapy and postmastectomy radiotherapy. Further, improved diagnostic abilities and surgical techniques, together with advances in treatment delivery, will help to increase the therapeutic ratio of radiotherapy. SUMMARY: There is increasing evidence for long-term benefits of radiotherapy for breast cancer and a reduction in the risks of late side effects in recent decades. This can have a profound impact on clinical practice in the future, leading to a broadening and individualizing of the indications for radiotherapy and improvements in patient survival.     

乳腺癌改良根治术后大分割放疗的研究

目的:探讨乳腺癌改良根治术后大分割放疗的疗效及不良反应。方法:2011年-2012年陕西省人民医院收治高危乳腺癌患者85例,行同侧胸壁和锁骨上下区照射,其中41例行大分割放疗（大分割组）,DT 42.56Gy／16f,总疗程22-24天;44例行常规分割放疗（常规组）,DT 50Gy／25f,总疗程33-35天。观察肿瘤的局部控制率、远处转移率及急性放疗反应的发生率。结果:中位随访时间为15个月,随访率为100％。全组2年生存率均为100％,无照射野内复发。大分割组和常规组远处转移率分别为12.2％、11.4％（χ2=0.039,P=0.843）。大分割组和常规组1级白细胞减少、2级放射性皮炎、2级放射性肺炎发生率分别为24.4％与27.3％（χ2=0.092,P=0.762 ）、17.1％与13.6％(χ2=0.194,P＝0.660)、 4.9％与6.8％(χ2=0.144,P=0.704)。结论:乳腺癌改良根治术后大分割放疗的近期疗效与常规分割相似,急性毒副反应可以接受。     

Comparison of Conventional and Hypofractionated Radiotherapy in Breast Cancer Patients in Terms of 5-Year Survival,Locoregional Recurrence,Late Skin Complications and Cosmetic Results

Bckground: Adjuvant radiation therapy is commonly administered following breast-conserving surgery for breast cancer patients. Hypofractionated radiotherapy can significantly reduce the waiting time for radiotherapy, working load on machines, patient visits to radiotherapy departments and medical costs. Material/Methods: Fifty-two patients with operable breast cancer (pT1-3pN0M0) who underwent breast conservation surgery in Tehran Cancer Institute during January 2011 to January 2012, were randomly assigned to undergo radiotherapy in two arms (hypofractionated radiotherapy arm with 30 patients, dose 42.5 Gy in 16 fractions; and conventional radiotherapy arm with 22 patients, dose 50 Gy in 25 fractions). W compared these two groups in terms of overall survival, locoregional control, late skin complications and cosmetic results. Results: At a median follow-up of 52.4 months (range: 0–64 months), the follow-up rate was 82.6%. Overall, after 60 months, there was no detectable significant differences between groups regarding cosmetic results (p = 0.857), locoregional control or survival. Conclusions: The results confirm that hypofractionated radiotherapy with a subsequent boost is as effective as conventional radiotherapy, is well-tolerated and can be used as an alternative treatment method following breast conservation surgery.     

A Systematic Overview of Radiation Therapy Effects in Cervical Cancer (Cervix Uteri)

A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for cervical cancer is based on data from 1 meta-analysis and 34 randomized trials. In total, 35 scientific articles are included, involving 7 952 patients. The results were compared with those of a similar overview from 1996 including 34 024 patients. The conclusions reached can be summarized in these points: There are limited scientific data supporting that postoperative pelvic radiotherapy improves disease-free survival in early cervical cancer. No firm conclusion can be drawn.There is moderate scientific evidence that external beam radiotherapy combined with brachytherapy gives a similar disease-free and overall survival rate as radical hysterectomy in early cervical cancer.There is strong scientific evidence that concomitant radiochemotherapy improves disease-free and overall survival compared to radiotherapy alone in early cervical cancer.The NCI has recently published an announcement stating that cisplantin-based chemotherapy should be used concomitantly with radiotherapy in cervical cancer. No solid documentation for this statement can be found concerning locally advanced stages (>IIB).There is a strong scientific evidence that cisplatin-based chemotherapy given concomitantly with radiotherapy is superior to concomitant chemotherapy with hydroxyurea.There is no scientific evidence to show that neoadjuvant chemotherapy followed by radiotherapy improves disease-free or overall survival compared to radiotherapy alone in patients with localized cervical cancer.There is moderate scientific evidence that high-dose-rate brachytherapy gives the same local control rate as low-dose-rate brachytherapy but with fewer rectal complications.     

A systematic overview of radiation therapy effects in cervical cancer (cervix uteri)

A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for cervical cancer is based on data from 1 meta-analysis and 34 randomized trials. In total, 35 scientific articles are included, involving 7 952 patients. The results were compared with those of a similar overview from 1996 including 34 024 patients. The conclusions reached can be summarized in these points: There are limited scientific data supporting that postoperative pelvic radiotherapy improves disease-free survival in early cervical cancer. No firm conclusion can be drawn. There is moderate scientific evidence that external beam radiotherapy combined with brachytherapy gives a similar disease-free and overall survival rate as radical hysterectomy in early cervical cancer. There is strong scientific evidence that concomitant radiochemotherapy improves disease-free and overall survival compared to radiotherapy alone in early cervical cancer. The NCI has recently published an announcement stating that cisplatin-based chemotherapy should be used concomitantly with radiotherapy in cervical cancer. No solid documentation for this statement can be found concerning locally advanced stages ( >IIB). There is a strong scientific evidence that cisplatin-based chemotherapy given concomitantly with radiotherapy is superior to concomitant chemotherapy with hydroxyurea. There is no scientific evidence to show that neoadjuvant chemotherapy followed by radiotherapy improves disease-free or overall survival compared to radiotherapy alone in patients with localized cervical cancer. There is moderate scientific evidence that high-dose-rate brachytherapy gives the same local control rate as low-dose-rate brachytherapy but with fewer rectal complications.     

Breast cancer in very young women

Aims

The purpose was to analyse the characteristics, treatment, recurrences and survival of very young women with breast cancer.

Methods

212 female breast cancer patients ≤35 years old were treated during 1997-2007. The median follow-up time was 78 months.

Results

117 patients had lymph node metastases and 14 distant metastases at diagnosis. 81 (38%) tumours were hormone receptor negative and 130 (65%) grade 3. HER2 positivity was seen in 47 (34%) and triple negativity in 35 (26%) of the 137 tumours with known HER2 status. 140 women were treated with mastectomy and 68 with breast conserving surgery. 163 patients received postoperative radiotherapy, 175 adjuvant chemotherapy, 95 endocrine therapy and 18 trastuzumab. 63 patients experienced a recurrence, of which 20 had only a locoregional recurrence. 10 (15%) of the women with breast conserving surgery experienced ipsilateral breast tumour recurrence while ipsilateral thoracic wall recurrence was seen in 8 patients (6%) after mastectomy. Seven of these eight patients did not receive postmastectomy radiotherapy. DFI was shorter in patients with hormone receptor positive tumours. At the end of follow-up 44 women had died. The 5-year OS was 80%.

Conclusions

The 5-year OS for young women has become better but is still lower than for all breast cancer patients. DFI was shorter in patients with hormone receptor positive disease. Locoregional recurrences were seen more often after breast conserving surgery.     

保乳治疗复发后的乳房再造研究现状

在全球范围内,保乳术及整形保乳术在乳腺癌外科治疗中逐渐被广泛应用。对于保乳术后同侧乳房局部复发患者,相当一部分因会选择补救性全乳切除,面临着乳房缺失问题。这部分患者因有胸壁放疗史,并多进行过系统治疗,因此行乳房再造时具有一定的特殊性,需引起手术医师的重视。为给予手术医师手术方案的制定提供线索与帮助,本文将从肿瘤学安全性、术后近远期并发症、术后美学效果方面对解救性乳房切除术联合即刻乳房再造进行综述。      

Influence of boost radiotherapy in patients with ductal carcinoma in situ breast cancer: a multicenter,retrospective study in Korea (KROG 11-04)

To estimate the effect of boost radiotherapy on local recurrence-free survival (LRFS) in patients with ductal carcinoma in situ (DCIS) breast cancer. We included patients from nine institutions who met the following criteria: having Tis, age 18 years or older, having breast conserving surgery (BCS) and radiotherapy within 12 weeks after surgery. From 1995 through 2006, 728 patients were analyzed retrospectively by the Korean Radiation Oncology Group. All patients received whole-breast radiation therapy (WBRT) after BCS. 232 patients (31.9 %) also received boost radiation therapy (RT) (median 10 Gy). After median follow-up of 82 months, 5-year LRFS was 98.4 % and 10-year LRFS was 95.8 % for all patients. There was no statistically significant difference of LRFS between the boost and no-boost groups. Nineteen (2.6 %) patients had ipsilateral breast recurrences, including 12 of invasive recurrence and 7 DCIS. The presence of the HER2 receptor was associated with more invasive recurrences. Nine (1.2 %) patients developed contralateral breast cancer, including six invasive breast cancer and three DCIS. In the multivariate analysis, only the margin status was a significant prognostic factor for LRFS. Boost RT was not associated with further improvement of local control in DCIS after BCS and WBRT. HER2 receptor-positive patients may need further treatment with the anti-HER2 agents.     

The efficacy of delayed radiotherapy for locoregionally recurrent postmastectomy breast cancer

Using the results from a randomized controlled trial of patients with operable breast cancer (aimed at assessing the need for immediate postmastectomy radiotherapy in patients with no histological evidence of nodal involvement on subpectoral node biopsy), it has been possible to study the effectiveness of salvage radiotherapy for recurrences in the group of patients who had not received postoperative radiotherapy. While only 1 of 43 patients (2.3%) showed progressive disease, there was a further in-field relapse in 16 of the remaining 42 patients (38%). Four of these patients were salvaged by systemic therapy. Ultimately, therefore, there was failure of delayed radiotherapy for locoregional control in 30% of patients. (However, the overall locoregional control in both arms of the trial was identical).     

A systematic overview of radiation therapy effects in prostate cancer

A systematic review of radiation therapy trials in prostate cancer has been performed according to principles adopted by the Swedish Council of Technology Assessment in Health Care (SBU). This synthesis of the literature is based on data from one meta-analysis, 30 randomized trials, many dealing with hormonal therapy, 55 prospective trials, and 210 retrospective studies. Totally the studies included 152,614 patients. There is a lack of properly controlled clinical trials in most important aspects of radiation therapy in prostate cancer. The conclusions reached can be summarized as follows: * There are no randomized studies that compare the outcome of surgery (radical prostatectomy) with either external beam radiotherapy or brachytherapy for patients with clinically localized low-risk prostate cancer. However, with the advent of widely accepted prognostic markers for prostate cancer (pre-treatment PSA, Gleason score, and T-stage), such comparisons have been made possible. There is substantial documentation from large single-institutional and multi-institutional series on patients with this disease category (PSA < 10, GS < or = 6, < or = T2b) showing that the outcome of external beam radiotherapy and brachytherapy is similar to those of surgery. * There is fairly strong evidence that patients with localized, intermediate risk, and high risk (pre-treatment PSA > or = 10 and/or GS > or = 7 and/or > T2) disease, i.e. patients normally not suited for surgery, benefit from higher than conventional total dose. No overall survival benefit has yet been shown. * Dose escalation to patients with intermediate-risk or high-risk disease can be performed with 3D conformal radiotherapy (photon or proton) boost, with Ir-192 high dose rate brachytherapy boost, or brachytherapy boost with permanent seed implantation. Despite an increased risk of urinary tract and/or rectal side effects, dose-escalated therapy can generally be safely delivered with all three techniques. * There is some evidence that 3D conformal radiotherapy results in reduced late rectal toxicity and acute anal toxicity compared with radiotherapy administered with non-conformal treatment volumes. * There is some evidence that postoperative external beam radiotherapy after radical prostatectomy in patients with pT3 disease prolongs biochemical disease-free survival and that the likelihood of achieving long-term DFS is higher when treatment is given in an adjuvant rather than a salvage setting. A breakpoint seems to exist around a PSA level of 1.0 ng/mL, above which the likelihood for eradication of the recurrence of cancer diminishes. * After prostatectomy, endocrine therapy prior to and during adjuvant radiotherapy may result in longer biochemical disease-free survival than if only adjuvant radiotherapy is given. No impact on overall survival has been shown. * There is fairly strong evidence that short-term endocrine therapy prior to and during radiotherapy results in increased disease-free survival, increased local control, reduced incidence of distant metastases, and reduced cause-specific mortality in patients with locally advanced disease. * There is some evidence that short-term endocrine therapy prior to and during radiotherapy results in increased overall survival in a subset (GS 2-6) of patients with locally advanced disease. * There is strong evidence that adjuvant endocrine treatment after curative radiotherapy results in improved local control, increased freedom from distant metastases, and increased disease-free survival in patients with loco-regionally advanced and/or high-risk disease. * There is moderately strong evidence that adjuvant endocrine treatment after radiotherapy results in longer overall survival compared with radiotherapy alone in patients with loco-regionally advanced disease.     

Uncontrolled local disease after salvage treatment for ipsilateral breast tumour recurrence.

AIM: Uncontrolled local disease (ULD) following breast conservation constitutes a clinical problem with a major impact on quality of life. The current study analysed the outcome following treatment of ipsilateral breast tumour recurrence (IBTR) and the risk for ULD with the aim to identify risk factors for ULD. METHODS: In a cohort of 5502 patients treated for invasive breast cancer Stage I-II with breast-conserving surgery 1976-1998 in Stockholm, 307 patients with subsequent IBTR were identified. The majority (n = 219) had received postoperative radiotherapy. Twenty-six per cent of the patients received adjuvant tamoxifen, for 2 or 5 years, and 9% received adjuvant polychemotherapy. Median follow-up time was 11(2-23) years. 50/307 patients developed ULD, defined as the appearance of clinically manifest invasive adenocarcinoma in the remaining breast or on the ipsilateral chest wall which could not be eradicated within 3 months of detection. Multivariate linear logistic regression was used in the statistical analysis to identify prognostic factors for ULD. RESULTS: Five years following the diagnosis of IBTR the cumulative incidence of ULD was 13%. Five independent risk factors for ULD were identified; non-surgical treatment of IBTR, disseminated disease concurrent with IBTR, axillary lymph node metastases (at primary breast conservation), time < 3 years between breast conservation and IBTR, no adjuvant endocrine therapy. Eighty-eight per cent of the patients were treated with salvage mastectomy (n = 207) or re-excision (n = 62). The cumulative incidence at 5 years of ULD following salvage mastectomy and salvage re-excision were 10% and 16% respectively compared to 32% among patients treated non-surgically. Following IBTR, the 5-year overall survival among patients with local control was 78% in contrast to 21% among patients with ULD. CONCLUSION: Uncontrolled local disease is an infrequent but important outcome following breast-conserving surgery. Primary postoperative radiotherapy reduces the risk for IBTR and is therefore recommended as part of the primary treatment to avoid both IBTR and ULD. In addition to radiotherapy, adjuvant therapy reduces the risk for IBTR and thereby the risk for subsequent ULD. Patients with IBTR, independent of concurrent distant metastases, should when feasible be recommended for salvage surgery as it provides superior local control compared to salvage systemic therapy alone.     

Cardiovascular death and second non-breast cancer malignancy after postmastectomy radiation and doxorubicin-based chemotherapy

PURPOSE: To assess the incidence of long-term toxicity after postmastectomy radiation and doxorubicin-based adjuvant chemotherapy. METHODS: Records of 470 patients treated with mastectomy, doxorubicin-based chemotherapy, and postmastectomy radiation in five institutional prospective trials were retrospectively reviewed. Actuarial toxicity rates were compared with those of 1031 patients treated with mastectomy and doxorubicin-based chemotherapy who did not receive postmastectomy radiation. For those treated with radiation, the chest wall received a median dose of 55 Gy with Co-60 (42%) or electrons (51%). Adjuvant chemotherapy consisted of a doxorubicin-based regimen, often followed by 2 years of cyclophosphamide, methotrexate, and fluorouracil. RESULTS: Median follow-up was 10 years. The overall 10-year actuarial rates of RTOG toxicity Grade >1 and >or=3 after radiation were 4% and 2%, respectively. The overall 10- and 15-year actuarial rates of second non-breast cancer malignancy were 3.8% and 7%, respectively. There was no statistical difference between the rates of non-breast cancer second malignancy in the radiated and unirradiated cohorts (3.4% vs. 4.7% 10-year actuarial rates). Increasing age and treatment with >10 cycles of chemotherapy were associated with higher rates of second malignancy (p = 0.025, p = 0.016). The 10-year actuarial rate of death from myocardial infarction (MI) was 2.4% (eight events) and 0.5% (five events) in the radiated and unirradiated groups, respectively (p = 0.058). Of the 8 irradiated patients who died of MI, 2 patients had left-sided breast cancer. CONCLUSIONS: We found very low rates of serious sequelae after postmastectomy radiation, including death from myocardial infarction and non-breast cancer second malignancy. The rate of second non-breast cancer malignancy was increased among patients treated with >10 cycles of cyclophosphamide-containing chemotherapy.     

Factors increasing local recurrence in breast-conserving surgery

From 20-year follow-up results of two pioneering randomized controlled trials demonstrating equal survival after mastectomy and breast-conservation therapy, recent high-quality, evidence-based clinical practice recommendations have been made. Breast-conservation therapy undoubtedly represents substantial progress for a better quality of life for women with early-stage breast cancer. However, lumpectomy is associated with a substantial proportion, approximately 10–20%, of local recurrence in long-term follow-up studies even after accounting for postoperative radiotherapy. Risk factors for local failure include margin status, young age and an extensive intraductal component. Young age and family history strongly suggest the need for genetic testing before initiation of treatment. Women with BRCA1 or BRCA2 mutations should be informed about the increased risk of contralateral breast cancer and ipsilateral failure after breast-conservation therapy. Bilateral mastectomy should also be offered as a treatment option. There is controversy over whether current effective adjuvant treatment, including chemotherapy and endocrine therapy, beyond appropriate local treatment as surgery and radiotherapy, can improve local control. Instead of debate over whether an ipsilateral tumor after breast-conservation therapy is local recurrence or a new primary cancer by analyzing conflicting data lacking strong evidence, efforts should be focused on reducing this risk irrespective of origin. Selecting women for breast-conservation therapy and achieving margin control can reduce ipsilateral failures.     

Factors increasing local recurrence in breast-conserving surgery

From 20-year follow-up results of two pioneering randomized controlled trials demonstrating equal survival after mastectomy and breast-conservation therapy, recent high-quality, evidence-based clinical practice recommendations have been made. Breast-conservation therapy undoubtedly represents substantial progress for a better quality of life for women with early-stage breast cancer. However, lumpectomy is associated with a substantial proportion, approximately 10-20%, of local recurrence in long-term follow-up studies even after accounting for postoperative radiotherapy. Risk factors for local failure include margin status, young age and an extensive intraductal component. Young age and family history strongly suggest the need for genetic testing before initiation of treatment. Women with BRCA1 or BRCA2 mutations should be informed about the increased risk of contralateral breast cancer and ipsilateral failure after breast-conservation therapy. Bilateral mastectomy should also be offered as a treatment option. There is controversy over whether current effective adjuvant treatment, including chemotherapy and endocrine therapy, beyond appropriate local treatment as surgery and radiotherapy, can improve local control. Instead of debate over whether an ipsilateral tumor after breast-conservation therapy is local recurrence or a new primary cancer by analyzing conflicting data lacking strong evidence, efforts should be focused on reducing this risk irrespective of origin. Selecting women for breast-conservation therapy and achieving margin control can reduce ipsilateral failures.