Rate Of Contralateral Breast Cancer Research Articles

Declining Incidence of Contralateral Breast Cancer in the United States From 1975 to 2006

Contralateral breast cancer (CBC) is the most frequent new malignancy among women diagnosed with a first breast cancer. Although temporal trends for first breast cancers have been well studied, trends for CBC are not so well established. We examined temporal trends in CBC incidence using US Surveillance, Epidemiology, and End Results database (1975 to 2006). Data were stratified by estrogen receptor (ER) status of the first breast cancer for the available time period (1990+). We estimated the annual percent change (EAPC) in CBC rates using Poisson regression models adjusted for the age at and time since first breast cancer diagnosis. Before 1985, CBC incidence rates were stable (EAPC, 0.27% per year; 95% CI, -0.4 to 0.9), after which they declined with an EAPC of -3.07% per year (95% CI, -3.5 to -2.7). From 1990 forward, the declines were restricted to CBC after an ER-positive cancer (EAPC, -3.18%; 95% CI, -4.2 to -2.2) with no clear decreases after an ER-negative cancer. Estimated current age-specific CBC rates (per 100/year) after an ER-positive first cancer were: 0.45 for first cancers diagnosed before age 30 years and 0.25 to 0.37 for age 30 years or older. Rates after an ER-negative cancer were higher: 1.26 before age 30 years, 0.85 for age 30 to 35 years, and 0.45 to 0.65 for age 40 or older. Results show a favorable decrease of 3% per year for CBC incidence in the United States since 1985. This overall trend was driven by declining CBC rates after an ER-positive cancer, possibly because of the widespread usage of adjuvant hormone therapies, after the results of the Nolvadex Adjuvant Trial Organisation were published in 1983, and/or other adjuvant treatments.

Influence of Margin Status on Outcomes in Lobular Carcinoma

We analyzed 382 patients with pure lobular carcinoma treated up to 2002 with sufficient follow-up to draw prognostic conclusions, all treated by conservative surgery. Our aim was to evaluate the influence of margin status on outcomes with a view assessing the appropriateness of conservative surgery in this breast cancer subtype. We assessed locoregional relapse, distant metastasis, contralateral breast cancer, breast cancer-related event free survival, disease-free survival and overall survival according to margin status categorized as at least 10 mm versus less than 10 mm (usually considered negative). The proportions of patients with less than 10 mm margins varied significantly with age (P = 0.02), menopausal status (P = 0.006), and tumor size (P = 0.02) but no other characteristic was significantly related to margin status. As regards unfavorable events during follow-up, none differed significantly between at least 10 mm and less than 10 mm margin groups. In particular, there were 11 (3.7%) local relapses in the same quadrant in at least 10 mm margin group compared to 4 (4.6%) in the less than 10 mm margin group, and 7 (2.4%) ipsilateral breast cancers in the 10 mm or more margin group but none in the less than 10 mm group. These findings indicate that minimal residual disease as evidenced by margins less than 10 mm is eradicated by radiotherapy (backed up in selected cases by reexcision, which in this series was always conservative). The rate of contralateral breast cancer was low at 2.9% indicating that prophylactic contralateral mastectomy is not justified. We conclude that the surgical approach and criteria for adjuvant hormonal and systemic treatment in lobular carcinoma should be the same as for ductal carcinoma, provided that adequate preoperative investigations exclude extensive multifocal and contralateral disease.

Abstract P4-10-04: Rates of Second Malignancies after Definitive Local Treatment for Ductal Carcinoma In Situ of the Breast

Abstract Background: We analyzed the risk of developing second malignancies in patients with ductal carcinoma in situ (DCIS) undergoing surgery and radiotherapy (S+RT) versus surgery alone (S). Material and Methods: The S+RT cohort consisted of 256 women treated with breast conserving therapy at William Beaumont Hospital. The S cohort consisted of 2,788 women with DCIS in the regional SEER database treated during the same time period. A matched-pair analysis was performed in which each S+RT patient was randomly matched with 8 S patients (total of 2048 patients). Matching criteria included age +/− 2 years. The rates of second malignancies were analyzed overall and as contralateral breast versus non-breast cancers and by organ system. Results: Median follow-up was 13.7 years for the S+RT cohort and 13.3 years for the S cohort. The overall 10-/15-year rate of second malignancies among the S+RT and S cohorts were 14.2%/24.2% and 16.4%/22.6%, respectively (p=0.668). The 15-year second contralateral breast cancer rate was 14.2% in the S+RT cohort and 10.3% in the S cohort (p=0.439). The 15- year risk of a second non-breast malignancy was 14.2% for the S+RT cohort and 13.4% for the S alone cohort (p=0.660). When analyzed by organ system, the 10- and 15-year rates of second malignancies did not differ between the S+RT and the S cohorts for pulmonary, gastrointestinal, central nervous system, gynecological, genitourinary, lymphoid, sarcomatoid, head and neck, or unknown primary tumors. Discussion: Compared with S alone, S +RT was not associated with an overall increased risk of second malignancies in women with DCIS. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-10-04.

Rates of Second Malignancies After Definitive Local Treatment for Ductal Carcinoma In Situ of the Breast

We analyzed the risk of second malignancies developing in patients with ductal carcinoma in situ (DCIS) undergoing surgery and radiotherapy (S+RT) vs. surgery alone. The S+RT cohort consisted of 256 women treated with breast-conserving therapy at William Beaumont Hospital. The surgery alone cohort consisted of 2,788 women with DCIS in the regional Surveillance, Epidemiology, and End Results database treated during the same time period. A matched-pair analysis was performed in which each S+RT patient was randomly matched with 8 surgery alone patients (total of 2,048 patients). Matching criteria included age±2 years. The rates of second malignancies were analyzed overall and as contralateral breast vs. non-breast cancers and by organ system. Median follow-up was 13.7 years for the S+RT cohort and 13.3 years for the surgery alone cohort. The overall 10-/15-year rates of second malignancies among the S+RT and surgery alone cohorts were 14.2%/24.2% and 16.4%/22.6%, respectively (p=0.668). The 15-year second contralateral breast cancer rate was 14.2% in the S+RT cohort and 10.3% in the surgery alone cohort (p=0.439). The 15-year risk of a second non-breast malignancy was 14.2% for the S+RT cohort and 13.4% for the surgery alone cohort (p=0.660). When analyzed by organ system, the 10- and 15-year rates of second malignancies did not differ between the S+RT and surgery alone cohorts for pulmonary, gastrointestinal, central nervous system, gynecologic, genitourinary, lymphoid, sarcomatoid, head and neck, or unknown primary tumors. Compared with surgery alone, S+RT is not associated with an overall increased risk of second malignancies in women with DCIS.

Contralateral risk-reducing mastectomy in young women

Contralateral risk-reducing mastectomy consists in the surgical removal of the contralateral breast to reduce the risk of breast cancer there [1]. Patients with unilateral primary breast cancer have an increased risk of developing a contralateral breast cancer [2]. In a large-scale study, Quan et al. [3] evaluated the incidence, stage and outcomes of women with contralateral synchronous (defined as tumors diagnosed within 12 months of the initial diagnosis) and metachronous (tumors diagnosed beyond 12 months after the initial diagnosis) breast cancer over a 9-year study period. In the 28,787 cases of breast cancer identified, the mean annual incidence of contralateral breast cancer was 0.1%, while the cumulative incidence of contralateral synchronous cancer was 2.1%, and the cumulative incidence of metachronous cancer was 1.2%. Using the Surveillance, Epidemiology and End Results database (SEER), Gao et al. [4] found that the 5-, 10-, 15-, and 20-year actuarial incidence of developing contralateral breast cancer was 3, 6, 9 and 12%, respectively. The average incidence of contralateral breast cancer per year of follow-up per patient was estimated at 0.6%. Based on these, and other retrospective studies, the incidence rate of contralateral breast cancer in breast cancer patients has been estimated to range from approximately 0.5 to 1.8% per year. Benefits of contralateral risk-reducing mastectomy

Long-term outcomes of breast cancer in women aged 30 years or younger, based on family history, pathology and BRCA1/BRCA2/TP53 status

Background:There are relatively few articles addressing long-term follow-up in women with breast cancer at very young ages.Methods:We have updated and extended our population-based analysis of breast cancer diagnosed at the age ⩽30 years in North-west England to include an extra 15 patients with mutation testing in BRCA1, BRCA2 and TP53, with 115 of 288 consecutive cases being tested. Kaplan–Meier curves were generated to assess overall survival, contralateral breast cancer and other second primaries.Results:Survival analysis of all 288 patients showed poor overall survival, although this improved from a 15-year survival of only 46% in those diagnosed between 1980 and 1989 to 58% in those diagnosed between 1990 and 1997 (P=0.05). Contralateral breast cancer rates were at a steady rate of 0.6 per 1000, although the rates in mutation carriers were ∼2 per 1000. Altogether, 16 BRCA1, 9 BRCA2 and 6 TP53 mutations have now been found among the 115 cases on whom DNA analysis has been performed. BRCAPRO accurately predicted the number of carriers for BRCA1 and BRCA2 and was sensitive and specific at the 10 and 20% threshold, respectively. However, BRCAPRO did not seem to give any weight to DCIS, which accounted for two BRCA1 carriers and three TP53 carriers and overpredicted mutations at the high end of the spectrum, with only 6 of 11 (54%) with a >90% probability having identifiable BRCA1/2 mutations.Interpretation:Rates of new primaries are predicted to some extent by mutation status. BRCAPRO is useful at determining those patients aged ⩽30 years to be tested.

Population-based study of contralateral prophylactic mastectomy and survival outcomes of breast cancer patients.

Despite increased demand for contralateral prophylactic mastectomy (CPM), the survival benefit of this procedure remains uncertain. We used the Surveillance, Epidemiology, and End Results database to identify 107 106 women with breast cancer who had undergone mastectomy for treatment between 1998 and 2003 and a subset of 8902 women who also underwent CPM during the same period. Associations between predictor variables and the likelihood of undergoing CPM were evaluated by use of chi(2) analyses. Risk-stratified (estrogen receptor [ER] status, stage, and age) adjusted survival analyses were performed by using Cox regression. Statistical tests were two-sided. In a univariate analysis, CPM was associated with improved disease-specific survival (hazard ratio [HR] of death = 0.63, 95% confidence interval [CI] = 0.57 to 0.69; P < .001). Risk-stratified analysis showed that this association was because of a reduction in breast cancer-specific mortality in women aged 18-49 years with stages I-II ER-negative cancer (HR of death = 0.68, 95% CI = 0.53 to 0.88; P = .004). Five year-adjusted breast cancer survival for this group was improved with CPM vs without (88.5% vs 83.7%, difference = 4.8%). Although rates of contralateral breast cancer among young women with stages I-II disease undergoing CPM were independent of ER status, women with ER-positive tumors in the absence of prophylactic mastectomy also had a lower overall risk for contralateral breast cancer than women with ER-negative tumors (0.46% vs 0.90%, difference = 0.44%; P < .001). CPM is associated with a small improvement in 5-year breast cancer-specific survival mainly in young women with early-stage ER-negative breast cancer. This effect is related to a higher baseline risk of contralateral breast cancer.

Age-Specific Incidence of Breast Cancer in Breast Cancer Survivors and Their First-Degree Relatives

The incidence rate of breast cancer in first-degree relatives of women with breast cancer has been hypothesized to become constant at a predetermined age in accordance with observations of a high, roughly constant incidence rate of contralateral breast cancer by age. We attempted to test this hypothesis in the Danish population with cancer registry data. We determined the age-specific incidence rates of contralateral breast cancer in Danish women who had a first breast cancer before they were 50 years of age and the rates of breast cancer among their first-degree female relatives during 1943 to 1999. The observed rates were tested for trends chi test or evaluated in Cox proportional hazard models. A high incidence rate of contralateral breast cancer was observed in women aged 25-44 years, followed by a decreasing rate, which reached a level corresponding to the rate per breast in the general female population at age 65. At ages older than the index patients age at diagnosis, their first-degree female relatives showed significantly increasing incidence rates of breast cancer by age, with a relatively constant absolute difference of 187 breast cancers per 100,000 person-years between the observed rates and the expected rates. The rate of contralateral breast cancer is particular high at young ages but the excess ebbs as the cohort ages, perhaps due to elimination of predisposed individuals at early ages from the cohort of survivors. First-degree relatives seem to share breast cancer susceptibility genes with the family proband resulting in a constant excess rate of breast cancer throughout life.

Breast-conserving surgery with or without radiotherapy in women with ductal carcinoma in situ: a meta-analysis of randomized trials

BackgroundTo investigate whether Radiation therapy (RT) should follow breast conserving surgery in women with ductal carcinoma in situ from breast cancer (DCIS) with objective of decreased mortality, invasive or non invasive recurrence, distant metastases and contralateral breast cancer rates. We have done a meta-analysis of these results to give a more balanced view of the total evidence and to increase statistical precision.MethodsA meta-analysis of randomized controlled trials (RCT) was performed comparing RT treatment for DCIS of breast cancer to observation. The MEDLINE, EMBASE, CANCERLIT, Cochrane Library databases, Trial registers, bibliographic databases, and recent issues of relevant journals were searched. Relevant reports were reviewed by two reviewers independently and the references from these reports were searched for additional trials, using guidelines set by QUOROM statement criteria.ResultsThe reviewers identified four large RCTs, yielding 3665 patients. Pooled results from this four randomized trials of adjuvant radiotherapy showed a significant reduction of invasive and DCIS ipsilateral breast cancer with odds ratio (OR) of 0.40 (95% CI 0.33 – 0.60, p < 0.00001) and 0.40 (95% CI 0.31 – 0.53, p < 0.00001), respectively. There was not difference in distant metastases (OR = 1.04, 95% CI 0.57–1.91, p = 0.38) and death rates (OR = 1.08, 95%CI 0.65 – 1.78, p = 0.45) between the two arms. There was more contralateral breast cancer after adjuvant RT (66/1711 = 3.85%) versus observation (49/1954 = 2.5%). The likelihood of contralateral breast cancer was 1.53-fold higher (95% CI 1.05 – 2.24, p = 0.03) in radiotherapy arms.ConclusionThe conclusion from our meta-analysis is that the addition of radiation therapy to lumpectomy results in an approximately 60% reduction in breast cancer recurrence, no benefit for survival or distant metastases compared to excision alone. Patients with high-grade DCIS lesions and positive margins benefited most from the addition of radiation therapy. It is not yet clear which patients can be successfully treated with lumpectomy alone; until further prospective studies answer this question, radiation should be recommended after lumpectomy for all patients without contraindications.

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.

Therapeutic radiation for breast cancer in BRCA mutation carriers and contralateral breast cancer (CBC) risk

611 Background: BRCA mutation carriers diagnosed with breast cancer are at high risk for contralateral second primary breast cancers. Mutations in BRCA1 and BRCA2 lead to defects in DNA repair. Radiation treatment for breast cancer is felt to increase risk of CBC, but the interaction between BRCA status and local radiation therapy with respect to their effects on CBC is unclear. Methods: Through an IRB approved database registry at the Cleveland Clinic, breast cancer patients tested for BRCA1 and BRCA2 mutations were identified and evaluated for CBC events and radiation treatment history. Patients with inadequate clinical follow-up, those with bilateral synchronous breast cancer and those undergoing bilateral mastectomy within one year of the original breast cancer diagnosis were excluded from the analysis. Chi-square test was used to compare CBC rates with or without prior radiation separately in patients testing positive and those testing negative for BRCA mutations. Results: Of 115 identified breast cancer patients tested for BRCA mutations, 57 met the inclusion criteria. Twenty-one carried BRCA1 or BRCA2 mutations and 36 tested negative for these mutations. Median follow-up for the two groups was 69.5 months (92 months in BRCA positive group and 51.5 months in BRCA negative group). Median age at diagnosis was 45 years (41 years in BRCA positive group and 48.5 in BRCA negative group). Among the 21 carriers, 9 patients (43%) developed CBC while only 3 of 36 patients (8%) testing negative for BRCA mutations developed CBC. Thirteen of 21 mutation carriers (62%) had received radiation treatment for the original cancer: CBC occurred in 3 of 13 (23%) radiated patients and 6 of 8 (75%) patients who had not received radiation (p= 0.02). Among 36 patients with negative BRCA testing, 30 (83%) had received radiation: CBC occurred in 3 of 30 (10%) mutation negative patients who had received prior radiation and in 0 of the 6 patients who had not received radiation (p = 0.42). Conclusions: CBC incidence was higher among BRCA mutation carriers than a control group suspected of having hereditary breast cancer but testing negative for these mutations. The use of radiation in the presence of a BRCA mutation, however, does not appear to further increase the risk for CBC. No significant financial relationships to disclose.

Age remains the first prognostic factor for loco-regional breast cancer recurrence in young (

Purpose To ascertain the loco-regional recurrence (LRR) rate and its major prognostic factors in patients younger than 40 and to determine the influence of age on the features of breast cancer and its treatment in two age groups: ⩽35 years and [36–39] years. Methods and materials Between 1985 and 1995, 209 premenopausal women, younger than 40, were treated for early breast cancers with primary breast conserving surgery followed by radiotherapy ± chemotherapy. Median age was 37 years with 66 patients (32%) ⩽35 years and 143 older (68%). Median follow-up was 12 years. Tumours’ characteristics were: cT1 in 75%, pN0 in 60%. Results LRR rate was 38% at 10 years, contralateral breast cancer rate 12%. Age was the only prognostic factor for LRR. The relative risk of LRR increased by 7% for every decreasing year of age. The annual risk of local recurrence peaked between 2 and 3 years after the initial diagnosis and returned to the level of contra-lateral breast cancer at 10 years. The younger population had infiltrating carcinomas that were significantly more commonly ductal, less commonly lobular, and of higher grade – they received chemotherapy more often. Conclusion Using conventional methods we could find no explanation as to why age remained the most important prognostic factor for breast cancer LRR. Known prognostic factors such as involved surgical margins seemed erased by adequate radiotherapy doses.

Outcomes of breast-conservation therapy for invasive lobular carcinoma are equivalent to those for invasive ductal carcinoma

Background Breast-conservation therapy (BCT), including wide local excision and postoperative irradiation, is considered standard treatment for early-stage invasive ductal carcinoma (IDC). The use of BCT in patients with invasive lobular carcinoma (ILC) has been questioned because of concerns regarding ipsilateral breast recurrence and risk of bilateral breast cancer. We evaluated our institutional experience with BCT and compared treatment outcomes for ILC with those for IDC. Methods A review of our BCT database revealed 84 patients with ILC and 1,126 with IDC with stage I or II disease treated with BCT and radiation between 1976 and 1999. We evaluated local-regional recurrence, disease-specific survival, and contralateral breast cancer rates in both groups. Results The 5- and 10-year local-regional recurrence rates for the ILC group were 1% and 7%, respectively, and 4% and 9%, respectively, for the IDC group ( P = .70). There were no significant differences in the 5- and 10-year disease-specific survival rates between the groups. Contralateral breast cancer occurred in 11.3% of patients with IDC and 11.9% of patients with ILC. Conclusions BCT achieves similar local-regional control and survival outcomes in selected patients with ILC or IDC. Breast-conservation therapy is an appropriate treatment strategy for patients with early-stage invasive lobular carcinoma.

NCIC CTG MA.17: Intent to treat analysis (ITT) of randomized patients after a median follow-up of 54 months

549 Background: MA.17 evaluated letrozole (LET) or placebo (PLAC) after 5 years of tamoxifen (Tam) and showed [median follow-up 30 months (mos)] significant improvement in disease-free survival (DFS) for LET [hazard ratio (HR) 0.57, p = 0.00008]. The trial was unblinded and PLAC patients (pts) were offered LET. An ITT analysis of all outcomes, before and after unblinding, based on the original randomization was performed. Methods: A stratified log-rank test was used to compare DFS, distant (D)DFS, overall survival (OS) and incidence of contra-lateral breast cancer (CBC). The Cox regression model used baseline stratification variables and two prespecified factors, menopausal status at the start of Tam and time on Tam. Subgroup analyses for DFS and OS were performed for the two prespecified subsets. All p-values were two-sided Results: 5187 pts were randomized at baseline and, at unblinding, 1655 of 2268 PLAC pts accepted LET. At median follow-up of 54 mos (range,16–86) 363 recurrences or CBC’s (144 LET and 219 PLAC) occurred; 118 LET and 176 PLAC pts had recurrent disease and 26 LET and 43 PLAC pts had CBC. 4 year DFS was 94.3% (LET) and 91.4% (PLAC) (HR 0.64; 95% CI, 0.52 - 0.79; p = 0.00002). Corresponding 4 year DDFS was 96.2% and 94.9% (HR 0.76; 0.58–0.99; p = 0.041). 4 year OS was 95.0% (LET) and 95.1% (PLAC) (HR 1.00; 0.78–1.28; p = 0.99). LET was equally effective in node +ve and -ve pts (i.e., similar HRs) in DFS. OS was not significantly different for LET and PLAC in any subgroup. The annual rate of CBC was 0.29% LET (0.18–0.40) and 0.47% PLAC (0.34–0.61); HR 0.61 (0.38–0.98) p = 0.037. 255 pts had died as of the data cut-off (128 LET and 127 PLAC). Conclusions: In this ITT analysis, pts originally randomized to LET within 3 months of stopping Tam did better than PLAC pts in DFS, DDFS and CBC, despite 73% of PLAC pts crossing to LET after unblinding. This highlights the strong beneficial effect of extended adjuvant therapy with LET. [Table: see text]

Long-Term Clinical Results of Whole Breast Irradiation with Prone Positioning

Purpose/Objective: To retrospectively evaluate tumor control and toxicity outcomes of breast conserving therapy (BCT) for DCIS and early-stage invasive breast cancer using whole breast radiotherapy delivered with prone positioning. Materials/Methods: Between 9/1992 and 8/2004, 248 patients with 251 breast cancers were treated using a previously described prone breast board with an aperture that allows the breast tissue to fall away from the chest wall. The target volume was clinically palpable breast tissue; no attempt was made to irradiate chest wall lymphatics. Prone position was preferred for patients with mobile, pendulous breast tissue, and those with comorbid cardiopulmonary disease. Patients receiving IMRT were not eligible. Median patient age was 60 yrs (range, 30–83 yrs) with 20% pre-menopausal. Tumor stages were Tis (n=35), T1 (n=185), and T2 (n=31). Infiltrating ductal carcinoma comprised 77% of cases with invasion. Mean tumor size was 1.3±0.8 cm. Final margins were close or positive in 8.8%. The axilla was surgically staged in 83% of cases, showing pN1 and pN2 status in 17% and 1%, respectively. Photon (6MV) fields with wedges treated the whole breast to 46–50.4 Gy. Tumor bed boosts of 10–18 Gy were delivered in 85% of cases. Adjuvant chemotherapy was administered to 42% of patients; 62% received hormonal therapy. Median follow-up was 59 months (range, 3–143 months). Results: Actuarial outcomes are shown in Table 1. All true local recurrences occurred within 4 years. Recurrences in other quadrants of the treated breast were rare before five years, and were similar to rates of contralateral breast cancer thereafter. There were no significant differences in IBTR rates for DCIS and invasive cancers. There were only two regional nodal relapses. Ten patients were able to receive BCT, for whom mastectomy had been recommended due to massive breasts, prior radiation, or significant pulmonary disease.Table 1Actuarial outcomes Treatment was well tolerated. Treatment breaks were needed for only 2% of patients. Acute grade 1–2 dermatitis and edema were seen in 80% and 70% of patients, respectively. Acute grade 3 dermatitis was seen in only 6% of patients. Eight patients (3.2%) complained of significant chest wall pain from lying on the prone breast board. Four of these patients (1.6%) had rib fractures by plain films. A ninth patient discontinued treatment after one fraction due to rib pain. Late effects were evaluable in 70% of cases. Grade 2 or higher skin and subcutaneous tissue toxicity were seen in only 6% and 18%, respectively. There were no late rib fractures. The treating physicians of 19 patients with severe comorbid cardiopulmonary disease did not report exacerbation of these conditions by radiotherapy. Conclusions: Prone position breast radiation results in excellent long-term disease control compared to historical series and demonstrates a favorable toxicity profile. These data suggest that incomplete coverage of the chest wall lymphatics does not adversely impact disease free survival, and provides further support for partial breast irradiation strategies. Previously published dosimetry studies demonstrate improved homogeneity and decreased lung and cardiac doses with this technique. The current data suggest that these improvements translate into reducing the toxicity of BCT.

Risk of breast cancer recurrence and contralateral breast cancer in relation to BRCA1 and BRCA2 mutation status following breast-conserving surgery and radiotherapy

BRCA1 and BRCA2 germline mutations are associated with a strong risk of breast cancer, which may preclude breast-conserving treatment in carriers. This study examined whether mutation status influenced the rate of breast cancer recurrence following breast-conserving treatment. BRCA1 and BRCA2 genes were screened for germline mutations in 131 patients with a family history of breast and/or ovarian cancer, who had been treated with breast-conserving surgery and radiotherapy. The 131 patients with familial history were matched to 261 patients without, according to age at diagnosis and year of treatment. The follow-up of controls was at least equal to the time-interval between diagnosis and genetic testing in familial cases. Matched cohorts were compared according to rates of breast cancer recurrence as first event and contralateral breast cancer using log-rank tests. BRCA1/2 mutations were found in 20.6% patients with a family history. Nineteen patients had a BRCA1 mutation and 8 had a BRCA2 mutation. Breast cancers in mutation carriers were more often grade III ( p < 10-4) and oestrogen receptor negative ( p = 0.005) than tumours in both non-carriers and controls. Median follow-up for all 392 patients was 8.75 years. No significant differences in breast cancer recurrence as first event were seen between BRCA1/2 tumours and controls ( p = 0.47), carriers and non-carriers with a family history ( p = 0.96), or non-carriers and controls ( p = 0.10). On multivariate analysis, age was the most important factor significantly predicting for breast cancer recurrence. The rate of contralateral breast cancer was significantly increased in all patients with a family history: BRCA1/2 carriers versus controls ( p = 0.0003), non-carriers versus controls ( p = 0.0034) and carriers versus non-carriers ( p = 0.02). At a 9-year median follow-up, the rate of ipsilateral breast cancer recurrence was not higher in BRCA1 and BRCA2 mutation carriers than in non-carriers with a family history or sporadic cases. These results support the hypothesis that breast tumours in BRCA carriers are more sensitive to radiation. Therefore, breast-conserving treatment can be offered to these patients. However, longer follow-up is needed to ensure that the rate of new primary cancer in the treated breast does not increase in the long-term.

Carcinome canalaire in situ du sein : Analyse de 882 cas

This study assesses the results of "current clinical practice" among 882 women treated in nine French Cancer Centers from 1985 to 1995 for pure ductal carcinoma in situ (DCIS) of the breast. Median age was 53 years (range 21-87); 177 (20%) patients underwent mastectomy (M), 190 (22%) conservative surgery alone (CS) and 515 (58%) conservative surgery with radiotherapy (CS + RT). The crude 7-year local relapse (LR) rates were 2%, 31% and 13% among the M, CS and CS+RT subgroups (p<0.0001). All four LR after M were invasive as well as 31 (52%) out of 59 and 40 (61%) out of 66 in the CS and CS+RT groups. Distant metastases occurred in 1%, 3% and 1% of the three treatment groups. No LR factors were found in the M group. Among women treated with CS, the 7-year LR rates were 36%, 31% and 30% among women aged 40 or less, 41 to 60 and 61 or more (NS). For women treated by CS+RT, the LR rates in these age subgroups were 33%, 13% and 8%, respectively (p<0.0001). Patients with negative, positive or uncertain margins had 7-year LR rates of 26%, 56% and 29% respectively if treated with CS (p=0.02) and 11%, 23% and 9% if treated with CS+RT (p=0.0008). RT reduced LR rates by 65% in all histological subgroups, but more particularly in comedocarcinoma and mixed cribriform/papillary subgroups. The 7-year rate of contralateral breast cancer was 7%, identical in all subgroups. Mastectomy remains the safest treatment for women with DCIS, with a 98% 7-year control rate. After conservative surgery, RT reduces very significantly LR rates, according to the NSABP B-17 and EORTC 10853 randomized trial results. The RT benefit is present in all clinical/histological subgroups, but its magnitude varies. Young age (<40 years) and incomplete excision are the most important LR risk factors.

Fifteen-year results of breast-conserving surgery and definitive irradiation for Stage I and II breast carcinoma: the University of Pennsylvania experience

Purpose To determine the 15-year outcomes for women with early stage breast cancer after breast conservation therapy. Methods and materials Between 1977 and 1990, 937 women with Stage I and II breast carcinoma (55% T1N0, 16% T2N0, 18% T1N1, and 11% T2N1) underwent lumpectomy, axillary lymphadenectomy, and definitive irradiation. The median patient age was 52 years. Of the 937 patients, 375 (40%) received adjuvant chemotherapy and/or hormonal therapy, including 249 (92%) of the 270 women with pathologically positive nodes. The median follow-up was 10.1 years. Results For the overall group, the 15-year overall survival rate was 71%, and the rate of freedom from distant metastases was 76%. The 15-year local failure rate was 19%. The 15-year contralateral breast cancer rate was 12%. The most common first events were distant failure (13%), local failure (10%), contralateral breast cancer (7%), and second malignant neoplasms (6%). The local failure rate at 10 years for favorable subsets of tumors characterized by mammographic detection, resection with negative margins, treatment with chemotherapy, and treatment with hormones was 8%, 10%, 10%, and 7%, respectively. Local failures were most commonly observed within (true recurrence), or just outside (marginal miss), the primary tumor bed (66%, 85 of 128). The rate of true recurrence or marginal miss at 5, 10, and 15 years was 5%, 10%, and 12%, respectively. Conclusion These high rates of survival and local control confirm that breast conservation therapy yields favorable results in women with early breast cancer into the second decade after treatment.

Risk of second primary cancer in the contralateral breast in women treated for early-stage breast cancer: A population-based study

Purpose To study the potential risk factors, including radiotherapy (RT) for contralateral breast cancer (CBC), in patients treated for early-stage breast cancer. Methods and materials The Surveillance, Epidemiology, and End Results database (1973–1996) was used to study the incidence of CBC after breast cancer. The Cox proportional hazards regression model was used to estimate the relative risk (RR) of CBC, with adjustment for confounders, including age, race, histologic subtype, and use of RT. Information on the use of hormonal therapy and chemotherapy was not available in the Surveillance, Epidemiology, and End Results database. Results A CBC was documented in 5679 (4.2%) of the 134,501 localized invasive or intraductal breast cancer patients surviving at least 3 months. The 10- and 20-year actuarial rate of CBC was 6.1% and 12%, respectively. In multivariate analysis, medullary carcinoma (RR = 1.18, 95% confidence interval [CI] 1.02–1.37), black race (RR = 1.20, 95% CI 1.08–1.33), and age >55 years at initial diagnosis (RR = 1.15, 95% CI 1.08–1.22) were associated with increased CBC risk. A total of 1234 (3.3%) of 37,379 patients who received RT developed CBC, and 4445 (4.6%) of 97,122 patients who did not receive RT developed CBC. Overall, RT was not associated with an increased risk of CBC (RR = 1.04, 95% CI 0.97–1.10) in multivariate analysis. The CBC risk associated with RT varied substantially with the length of follow-up. During the first 5 years of follow-up, RT was not associated with an increased CBC risk (age-adjusted RR = 0.96, 95% CI 0.88–1.04). For patients surviving for >5 years, RT was associated with a 14% increase in CBC risk (RR = 1.14, 95% CI 1.03–1.26). The increased CBC risk with RT was evident in patients aged <45 years (RR = 1.32, p = 0.01) and >55 years (RR = 1.15, p = 0.04) at initial diagnosis. The 5-, 10-, 15-, and 20-year actuarial rate of CBC was 2.9%, 6.5%, 10.2%, and 13.4%, respectively, for patients with RT; the corresponding rates were 3.0%, 6.0%, 8.9%, and 11.8% for patients without RT. The absolute increase in CBC risk associated with RT was 0.5%, 1.3%, and 1.6% in the 10-, 15-, and 20-year actuarial rate, respectively. Conclusion CBC is not uncommon after breast cancer, especially for certain subsets of patients. RT was associated with a very small increased long-term CBC risk. This minimal increase in CBC risk should not affect clinical decision-making in treatment selection for patients with localized invasive breast cancer or ductal carcinoma in situ. Unnecessary radiation exposure to the contralateral breast should be avoided for all patients with early-stage breast cancer.

Section 5. Breast: Breast conserving treatment without radiotherapy

Radiotherapy (RT) is not always necessary for the prevention of ipsilateral breast recurrence in cases where cancer is not detected in the remaining breast tissue after breast conserving surgery. In addition, under these circumstances, the rate of a second primary cancer of the remaining breast is theoretically equal to the rate of contralateral breast cancer. In performing breast conserving treatment (BCT) at our institution we do not treat with RT if a strict serial pathological examination of the specimen (every 5 mm) reveals that the case has been safely resected (negative surgical margins). From 1986 to 1998, 827 patients (157 were ductal carcinoma in situ, and 670 were invasive) underwent BCT without RT at the Cancer Institute Hospital. Ipsilateral breast cancer was observed in 46 cases or 5.6% (0.85% annually) during a median observation period of 67 months. Of these 46 cases, 19 (2.3%) were diagnosed as a recurrence and 27 cases (3.3%) were second primary cancers. This recurrence rate is equivalent to the rate observed in 406 cases of BCT (1.7%) that were treated with RT. Most of these cases had shown positive surgical margins. Furthermore, the rate of occurrence of second cancers is not significantly different from the rate of occurrence of contralateral breast cancers. These results suggest that, by selecting irradiation cases based on careful pathological examinations, BCT can be safely performed.