To evaluate the volume of nodal irradiation associated with breast-conserving therapy, we defined the anatomic relationship of sentinel lymph nodes and axillary level I and II lymph nodes in patients ...receiving tangential breast irradiation.
A retrospective analysis of 65 simulation fields in women with breast cancer treated with sentinel lymph node surgery and 39 women in whom radiopaque clips demarcated the extent of axillary lymph node dissection was performed. We measured the relationship of the surgical clips to the anatomic landmarks and calculated the percentage of prescribed dose delivered to the sentinel lymph node region.
A cranial field edge 2.0 cm below the humeral head the sentinel lymph node region was included or at the field edge in 95% of the cases and the entire extent of axillary I and II dissection in 43% of the axillary dissection cases. In the remaining 57%, this field border encompassed an average of 80% of cranial/caudal extent of axillary level I and II dissection. In 98.5% of the cases, all sentinel lymph nodes were anterior to the deep field edge and 71% were anterior to the chest wall-interface, whereas 61% of the axillary dissection cohort had extension deep to the chest wall-lung interface. If the deep field edge had been set 2 cm below the chest wall-lung interface, the entire axillary dissection would have been included in 82% of the cases, and the entire sentinel lymph node would have been covered with a 0.5-cm margin. The median dose to the sentinel lymph node region was 98% of the prescribed dose.
By extending the cranial border to 2 cm below the humeral head and 2 cm deep to the chest wall-lung interface, the radiotherapy fields used to treat the breast can include the sentinel lymph node region and most of axillary levels I and II.
Purpose: The objective of this study was to evaluate the influence of pathologic factors other than tumor size and number of involved axillary nodes on the risk of locoregional recurrence (LRR) ...following mastectomy.
Patients and Methods: We reviewed the medical records of 1031 patients treated with mastectomy and doxorubicin-based chemotherapy without radiation on 5 prospective clinical trials. Median follow-up was 116 months (range, 6–262 months).
Results: Patients with gross multicentric disease were at increased risk of LRR (37% at 10 years). However, patients with multifocal disease and those with microscopic multicentric disease did not experience higher rates of LRR than those with single lesions (17% at 10 years). Patients with lymph-vascular space invasion (LVSI) or involvement of the skin or nipple also experienced high rates of LRR (25%, 32%, and 50%, respectively).
The presence of close (<5 mm) or positive margins was associated with an increased risk of LRR (45%). The increased risk of LRR observed for patients with pectoral fascial invasion (33%) was not reduced when negative deep margins were obtained.
On multivariate analysis, the presence of 4 or more involved axillary nodes, tumor size of greater than 5 cm, close or positive surgical margins, and gross multicentric disease were found to be independent predictors of LRR (all,
p < 0.01). In a separate analysis including only patients with 1–3 involved axillary nodes, microscopic invasion of the skin or nipple, pectoral fascial invasion, and the presence of close or positive margins were significant predictors of LRR.
Conclusion: In addition to the extent of primary and nodal disease, other factors that predict for high rates of LRR include the presence of LVSI, involvement of the skin, nipple or pectoral fascia, close or positive margins, or gross multicentric disease. These factors predict for high LRR rates regardless of the number of involved axillary nodes.
To investigate the incidence and local control of internal mammary lymph node metastases (IMN+) in patients with clinical N2 or N3 locally advanced breast cancer.
We retrospectively reviewed the ...records of 809 breast cancer patients diagnosed with advanced nodal disease (clinical N2-3) who received radiation treatment at our institution from January 2000 December 2006. Patients were considered IMN+ on the basis of imaging studies.
We identified 112 of 809 patients who presented with IMN+ disease (13.8%) detected on ultrasound, computed tomography (CT), positron emission tomography/CT (PET/CT), and/or magnetic resonance imaging (MRI) studies. All 112 patients with IMN+ disease received anthracycline and taxane-based chemotherapy. Neoadjuvant chemotherapy (NCT) resulted in a complete response (CR) on imaging studies of IMN disease in 72.1% of patients. Excluding 16 patients with progressive disease, 96 patients received adjuvant radiation to the breast or the chest wall and the regional lymphatics including the IMN chain with a median dose of 60 Gy if the internal mammary lymph nodes normalized after chemotherapy and 66 Gy if they did not. The median follow-up of surviving patients was 41 months (8-118 months). For the 96 patients able to complete curative therapy, the actuarial 5-year IMN control rate, locoregional control, overall survival, and disease-free survival were 89%, 80%, 76%, and 56%.
Over ten percent of patients with advanced nodal disease will have IMN metastases on imaging studies. Multimodality therapy including IMN irradiation achieves excellent rates of control in the IMN region and a DFS of more than 50% after curative treatment.
To evaluate how implementation of the 2003 American Joint Committee on Cancer (AJCC) staging system will affect stage-specific survival of breast cancer patients.
Records of 1,350 patients treated on ...sequential institutional protocols with mastectomy and adjuvant doxorubicin-based chemotherapy were reviewed. Pathologic stage was assigned retrospectively according to the 1988 and the 2003 AJCC staging criteria. Overall stage-specific survival (OS) was calculated using the Kaplan-Meier method, and hypothetical differences were compared by the log-rank test.
Six hundred five of 1,087 patients with stage II disease according to the 1988 classification system had stage II disease according to the 2003 system. The 10-year OS for patients with stage II disease was significantly improved using the 2003 system (76% 2003 v 65% 1988; P <.0001). Two hundred eighty-nine of 633 patients with stage IIb disease using the 1988 system were stage IIb with the 2003 system, and 10-year OS was 58% (1988) versus 70% (2003; P =.003). The number of patients with stage III disease increased from 207 (1988) to 443 (2003), and the 10-year OS changed from 45% (1988) to 50% (2003; P =.077). Most of this difference resulted from changes within stage IIIa: OS, 45% (1988) versus 59% (2003; P <.0001).
Stage reclassification using the new AJCC staging system for breast cancer will result in significant changes in reported outcome by stage. It is imperative that careful attention is devoted to this effect so that accurate conclusions regarding the efficacy of new treatment strategies can be drawn.
The first high-quality clinical trial to support ultrahypofractionated whole-breast irradiation (ultra-HF-WBI) for invasive early-stage breast cancer (ESBC) was published in April 2020, coinciding ...with the beginning of the COVID-19 pandemic. We analyzed adoption of ultra-HF-WBI for ductal carcinoma in situ (DCIS) and ESBC at our institution after primary trial publication.
We evaluated radiation fractionation prescriptions for all patients with DCIS or ESBC treated with WBI from March 2020 to May 2021 at our main campus and regional campuses. Demographic and clinical characteristics were extracted from the electronic medical record. Treating physician characteristics were collected from licensure data. Hierarchical logistic regression models identified factors correlated with adoption of ultra-HF-WBI (26 Gy in 5 daily factions UK-FAST-FORWARD or 28.5 Gy in 5 weekly fractions UK-FAST).
Of 665 included patients, the median age was 61.5 years, and 478 patients (71.9%) had invasive, hormone-receptor-positive breast cancer. Twenty-one physicians treated the included patients. In total, 249 patients (37.4%) received ultra-HF-WBI, increasing from 4.3% (2 of 46) in March-April 2020 to a high of 45.5% (45 of 99) in July-August 2020 (P < .001). Patient factors associated with increased use of ultra-HF-WBI included older age (≥50 years old), low-grade WBI without inclusion of the low axilla, no radiation boost, and farther travel distance (P < .03). Physician variation accounted for 21.7% of variance in the outcome, with rate of use of ultra-HF-WBI by the treating physicians ranging from 0% to 75.6%. No measured physician characteristics were associated with use of ultra-HF-WBI.
Adoption of ultra-HF-WBI at our institution increased substantially after the publication of randomized evidence supporting its use. Ultra-HF-WBI was preferentially used in patients with lower risk disease, suggesting careful selection for this new approach while long-term data are maturing. Substantial physician-level variation may reflect a lack of consensus on the evidentiary standards required to change practice.
This study compared the use of the internal mammary and thoracodorsal recipient vessels in a uniform group of patients who underwent delayed TRAM flap reconstruction after radiotherapy, focusing on ...usability rates and outcomes. The authors identified 123 delayed TRAM flap patients who had undergone postmastectomy radiotherapy from a prospective database (1990 to 2001). Recipient vessel unusability rates were calculated on the basis of reports of inspection of a vessel, either by direct intraoperative dissection or by findings from color Doppler examination (internal mammary vessels only). Charts were reviewed for outcomes including flap loss, vascular complications, fat necrosis, and lymphedema; t-test and chi-square analyses were performed to compare outcomes and unusability rates, and multiple regression analysis was performed to determine factors influencing outcome. Of the 123 planned free TRAM flaps, 106 were completed as free flaps and 17 were performed as pedicled flaps because of unusable recipient vessels. Of the free flaps, 45 were anastomosed to the internal mammary vessels, 55 to the thoracodorsal vessels, and six to other vessels. The internal mammary and thoracodorsal groups did not differ significantly in body mass index, abdominal scars, smoking history, time delay between irradiation and TRAM flap reconstruction, or flap ischemia time. Radiation doses to the axilla (thoracodorsal), internal mammary chain, and supraclavicular fossa were similar between the groups. The internal mammary vessels were rejected in 11 (20 percent) of 56 cases, and the thoracodorsal vessels were rejected in 19 (26 percent) of 74 cases (p = 0.42). In cases with unusable internal mammary vessels, 46 percent (n = 5) had inadequate veins, 27 percent (n = 3) had inadequate arteries, and in 27 percent (n = 3) both vessels were inadequate. In the 19 cases with unusable thoracodorsal vessels, 84 percent (n = 16) were excessively scarred, 11 percent (n = 2) had inadequate vessels, and 5 percent (n = 1) were absent. Outcomes were similar regardless of recipient vessels used (internal mammary versus thoracodorsal): total flap loss, 0 percent versus 4 percent (p = 0.20); vascular complications, 6.7 percent versus 11 percent (p = 0.46); arm lymphedema, 4.4 percent versus 9 percent (p = 0.37); partial flap loss, 9 percent versus 6 percent (p = 0.54); and fat necrosis, 18 percent versus 15 percent (p = 0.69). Multivariate analysis revealed a trend for higher complication rates in smokers and with the use of the thoracodorsal vessels as the recipients. Overall, no discernible unusability or outcome differences were detected between the internal mammary and thoracodorsal groups.
To our knowledge, NRG/RTOG 9804 is the only randomized trial to assess the impact of whole breast irradiation (radiation therapy RT) versus observation (OBS) in women with good-risk ductal carcinoma ...in situ (DCIS), following lumpectomy. Long-term results focusing on ipsilateral breast recurrence (IBR), the primary outcome, are presented here.
Eligible patients underwent lumpectomy for DCIS that was mammogram detected, size ≤ 2.5 cm, final margins ≥ 3 mm, and low or intermediate nuclear grade. Consented patients were randomly assigned to RT or OBS. Tamoxifen use was optional. Cumulative incidence was used to estimate IBR, log-rank test and Gray's test to compare treatments, and Fine-Gray regression for hazard ratios (HRs).
A total of six hundred thirty-six women were randomly assigned from 1999 to 2006. Median age was 58 years and mean pathologic DCIS size was 0.60 cm. Intention to use tamoxifen was balanced between arms (69%); however, actual receipt of tamoxifen varied, 58% RT versus 66% OBS (
= .05). At 13.9 years' median follow-up, the 15-year cumulative incidence of IBR was 7.1% (95% CI, 4.0 to 11.5) with RT versus 15.1% (95% CI, 10.8 to 20.2) OBS (
= .0007; HR = 0.36; 95% CI, 0.20 to 0.66); and for invasive LR was 5.4% (95% CI, 2.7 to 9.5) RT versus 9.5% (95% CI, 6.0 to 13.9) OBS (
= .027; HR = 0.44; 95% CI, 0.21 to 0.91). On multivariable analysis, only RT (HR = 0.34; 95% CI, 0.19 to 0.64;
= .0007) and tamoxifen use (HR = 0.45; 95% CI, 0.25 to 0.78;
= .0047) were associated with reduced IBR.
RT significantly reduced all and invasive IBR for good-risk DCIS with durable results at 15 years. These results are not an absolute indication for RT but rather should inform shared patient-physician treatment decisions about ipsilateral breast risk reduction in the long term following lumpectomy.
Background Breast-conserving surgery (BCS) followed by radiotherapy is as effective as mastectomy for treatment of early invasive breast cancer. But earlier studies report low BCS use rates of 12% to ...43% nationally, especially in older patients. We sought to determine current patterns and predictors of BCS use. Study Design In a national Medicare database of all beneficiaries (age greater than 65 years) with incident invasive breast cancer treated with operation in 2003, claims codes identified BCS versus mastectomy and demographic, treatment, and geographic region covariates. The 2003 Area Resource File provided socioeconomic covariates. Logistic regression modeled predictors of BCS. Results In 56,725 women, 59% were treated with BCS versus 41% with mastectomy. BCS was more likely in women who were younger than 70 years (odds ratio OR, 1.37; 95% CI, 1.31 to 1.44; p < 0.001) and had lymph node-negative disease (OR, 1.60; 95% CI, 1.52 to 1.68; p < 0.001). Socioeconomic factors influenced use, with BCS more likely in areas with low poverty (OR, 1.05; 95% CI, 1.00 to 1.09; p = 0.03), high education (OR, 1.13; 95% CI, 1.08 to 1.19), high density of radiation oncologists (OR, 1.30; 95% CI, 1.06 to 1.59), and in metropolitan areas (OR, 1.20; 95% CI, 1.14 to 1.26). Significant geographic variation existed: 70% of women were treated with BCS in northeastern New England compared with only 48% to 50% in the South (p < 0.001). Conclusions Currently, more than half of older women across the US diagnosed with nonmetastatic invasive breast cancer treated surgically receive BCS, representing a substantial increased use compared with historical data. Lack of BCS use appears in part associated with socioeconomic disadvantage, suggesting that persistent barriers to breast conservation exist.
This study investigates the importance of the intracellular ratio of the two estrogen receptors ERα and ERβ for the ultimate potential of the phytoestrogens genistein and quercetin to stimulate or ...inhibit cancer cell proliferation. This is of importance because (i) ERβ has been postulated to play a role in modulating ERα-mediated cell proliferation, (ii) genistein and quercetin may be agonists for both receptor types and (iii) the ratio of ERα to ERβ is known to vary between tissues. Using human osteosarcoma (U2OS) ERα or ERβ reporter cells it was shown that compared to estradiol (E2), genistein and quercetin have not only a relatively greater preference for ERβ but also a higher maximal potential for activating ERβ-mediated gene expression. Using the human T47D breast cancer cell line with tetracycline-dependent ERβ expression (T47D-ERβ), the effect of a varying intracellular ERα/ERβ ratio on E2- or pythoestrogen-induced cell proliferation was characterised. E2-induced proliferation of cells in which ERβ expression was inhibited was similar to that of the T47D wild type cells, whereas this E2-induced cell proliferation was no longer observed when ERβ expression was increased. With increased expression of ERβ the phytoestrogen-induced cell proliferation was also reduced. These results point at the importance of the cellular ERα/ERβ ratio for the ultimate effect of (phyto)estrogens on cell proliferation.
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