The lateral decubitus breast boost: description, rationale, and efficacy.

PURPOSE: To describe and evaluate the modified lateral decubitus boost, a breast irradiation technique. Patients are repositioned and resimulated for electron boost to minimize the necessary depth for the electron beam and optimize target volume coverage. METHODS AND MATERIALS: A total of 2,606 patients were treated with post-lumpectomy radiation at our institution between January 1, 2000, and February 1, 2008. Of these, 231 patients underwent resimulation in the lateral decubitus position with electron boost. Distance from skin to the maximal depth of target volume was measured in both the original and boost plans. Age, body mass index (BMI), boost electron energy, and skin reaction were evaluated. RESULTS: Resimulation in the lateral decubitus position reduced the distance from skin to maximal target volume depth in all patients. Average depth reduction by repositioning was 2.12 cm, allowing for an average electron energy reduction of approximately 7 MeV. Mean skin entrance dose was reduced from about 90% to about 85% (p < 0.001). Only 14 patients (6%) experienced moist desquamation in the boost field at the end of treatment. Average BMI of these patients was 30.4 (range, 17.8-50.7). BMI greater than 30 was associated with more depth reduction by repositioning and increased risk of moist desquamation. CONCLUSIONS: The lateral decubitus position allows for a decrease in the distance from the skin to the target volume depth, improving electron coverage of the tumor bed while reducing skin entrance dose. This is a well-tolerated regimen for a patient population with a high BMI or deep tumor location.

Multileaf field-in-field forward-planned intensity-modulated dose compensation for whole-breast irradiation is associated with reduced contralateral breast dose: a phantom model comparison.

PURPOSE: Static multileaf collimated field-in-field forward-planned intensity-modulated radiation treatment (FiF-IMRT) has been shown to improve dose homogeneity compared to conventional wedged fields. However, a direct comparison of the scattered dose to the contralateral breast resulting from wedged and FiF-IMRT plans remains to be documented. METHODS: The contralateral scattered breast dose was measured in a custom-designed anthropomorphic breast phantom in which 108 thermoluminescent dosimeters (TLDs) were volumetrically placed every 1-2cm. The target phantom breast was treated to a dose of 50Gy using three dose compensation techniques: No medial wedge and a 30-degree lateral wedge (M0-L30), 15-degree lateral and medial wedges (M15-L15), and FiF-IMRT. TLD measurements were compared using analysis of variance. RESULTS: For FiF-IMRT, the mean doses to the medial and lateral quadrants of the contralateral breast were 112cGy (range 65-226cGy) and 40cGy (range 18-91 cGy), respectively. The contralateral breast doses with FiF-IMRT were on average 65% and 82% of the doses obtained with the M15-L15 and M0-L30 techniques, respectively (p<0.001). Compared to the M15-L15 technique, the maximum dose reduction obtained with FiF-IMRT was 115cGy (range 13-115cGy). CONCLUSIONS: The dose to the contralateral breast is significantly reduced with FiF-IMRT compared to wedge-compensated techniques. Although long-term follow-up is needed to establish the clinical relevance of this finding, these results, along with the previously reported improvement in ipsilateral dose homogeneity, support the use of FiF-IMRT if resources permit.

African-American race is associated with a poorer overall survival rate for breast cancer patients treated with mastectomy and doxorubicin-based chemotherapy.

BACKGROUND: African-American (AA) race has been associated with a worse outcome in breast cancer. It is unclear whether this is due to biological factors, socioeconomic factors, or both. METHODS: The records from 2 independent cohorts of breast cancer patients treated on institutional protocols with mastectomy and adjuvant (n = 1456) or neoadjuvant (n = 684) doxorubicin-based chemotherapy were retrospectively reviewed. RESULTS: The adjuvant (Adj) chemotherapy cohort included 1142 Caucasian (CA), 186 Hispanic (HI), and 128 (AA) patients. The neoadjuvant (Neo) chemotherapy protocols included 448 CA, 114 HI, and 122 AA patients. In both groups, AA patients had later-stage tumors (Adj P = .017; Neo P = .051), a higher rate of estrogen receptor (ER)-negative disease (Adj P = .054; Neo P = .039), and a worse 10-year actuarial overall survival rate than CA or HI patients (Adj, 52%, 62%, and 62%, respectively, P = .009; Neo, 40%, 50%, and 56%, respectively, P = .015). In multivariate analyses, AA race remained independently associated with a poorer overall survival rate in both cohorts (Adj, hazard ratio = 1.39, P = .018; Neo, hazard ratio = 1.37, P = .02). CONCLUSIONS: The data suggest that AA race is associated with less favorable biological tumor features, such as an increased likelihood of ER-negative disease, than those found in CA and HI patients. Such differences in tumor biology, as well as previously described socioeconomic factors, likely contribute to the lower rate of survival in the AA breast cancer population.

Fifteen-year results of a randomized prospective trial of hyperfractionated chest wall irradiation versus once-daily chest wall irradiation after chemotherapy and mastectomy for patients with locally advanced noninflammatory breast cancer.

PURPOSE: To analyze the results of a Phase III clinical trial that investigated whether a hyperfractionated radiotherapy (RT) schedule could reduce the risk of locoregional recurrence in patients with locally advanced breast cancer treated with chemotherapy and mastectomy. METHODS AND MATERIALS: Between 1985 and 1989, 200 patients with clinical Stage III noninflammatory breast cancer were enrolled in a prospective study investigating neoadjuvant and adjuvant chemotherapy. Of the 179 patients treated with mastectomy after neoadjuvant chemotherapy, 108 participated in a randomized component of the trial that compared a dose-escalated, hyperfractionated (twice-daily, b.i.d.) chest wall RT schedule (72 Gy in 1.2-Gy b.i.d. fractions) with a once-daily (q.d.) schedule (60 Gy in 2-Gy q.d. fractions). In both arms of the study, the supraclavicular fossa and axillary apex were treated once daily to 50 Gy. The median follow-up period was 15 years. RESULTS: The 15-year actuarial locoregional recurrence rate was 7% for the q.d. arm and 12% for the b.i.d. arm (p=0.36). The rates of severe acute toxicity were similar (4% for q.d. vs. 5% for b.i.d.), but moist desquamation developed in 42% of patients in the b.i.d. arm compared with 28% of the patients in the q.d. arm (p=0.16). The 15-year actuarial rate of severe late RT complications did not differ between the two arms (6% for q.d. vs. 11% for b.i.d., p=0.54). CONCLUSION: Although the sample size of this study was small, we found no evidence that this hyperfractionation schedule of postmastectomy RT offered a clinical advantage. Therefore, we have concluded that it should not be further studied in this cohort of patients.

Immediate breast reconstruction can impact postmastectomy irradiation.

OBJECTIVE: Immediate breast reconstruction is an attractive option for patients who undergo mastectomy. The purpose of this study was to qualitatively assess the effect of immediate reconstruction on the design of postmastectomy radiotherapy fields at our institution. METHODS: We retrospectively reviewed the records of 152 patients treated at our institution with postmastectomy radiotherapy over a 1-year period. We identified 18 postmastectomy radiotherapy plans in the setting of prior reconstruction. By consensus, 2 board-certified radiation oncologists scored the 18 plans in terms of 4 outcomes: coverage of the chest wall breadth, coverage of the ipsilateral internal mammary chain (IMC) region, minimization of lung exposure, and avoidance of the heart. RESULTS: Only 4 of the 18 plans resulted in optimal treatment of the chest wall breadth and IMC region while well avoiding the heart and lung. Of the remaining 14 plans, 12 compromised coverage of the chest wall breadth medially and/or laterally, and 9 provided no IMC coverage. CONCLUSION: Immediate breast reconstruction may impose limitations on the treatment planning of postmastectomy radiotherapy, particularly in regard to providing broad coverage of the chest wall and IMC region while avoiding excess exposure of the heart and lung.

Clinical investigation: regional nodal failure patterns in breast cancer patients treated with mastectomy without radiotherapy.

PURPOSE: The purpose of this study was to describe regional nodal failure patterns in patients who had undergone mastectomy with axillary dissection to define subgroups of patients who might benefit from supplemental regional nodal radiation to the axilla or supraclavicular fossa/axillary apex. METHODS AND MATERIALS: The cohort consisted of 1031 patients treated with mastectomy (including a level I-II axillary dissection) and doxorubicin-based systemic therapy without radiation on five clinical trials at M.D. Anderson Cancer Center. Patient records, including pathology reports, were retrospectively reviewed. All regional recurrences (with or without distant metastasis) were recorded. Median follow-up was 116 months (range, 6-262 months). RESULTS: Twenty-one patients recurred within the low-mid axilla (10-year actuarial rate 3%). Of these, 16 were isolated regional failures (no chest wall failure). The risk of failure in the low-mid axilla was not significantly higher for patients with increasing numbers of involved nodes, increasing percentage of involved nodes, larger nodal size or gross extranodal extension. Only 3 of 100 patients with <10 nodes examined recurred in the low-mid axilla. Seventy-seven patients had a recurrence in the supraclavicular fossa/axillary apex (10-year actuarial rate 8%). Forty-nine were isolated regional recurrences. Significant predictors of failures in this region included > or = 4 involved axillary lymph nodes, >20% involved axillary nodes, and the presence of gross extranodal extension (10-year actuarial rates 15%, 14%, and 19%, respectively, p < 0.0005). The extent of axillary dissection and the size of the largest involved node were not predictive of failure within the supraclavicular fossa/axillary apex. CONCLUSIONS: These results suggest that failure in the level I-II axilla is an uncommon occurrence after modified radical mastectomy and chemotherapy. Therefore, supplemental radiotherapy to the dissected axilla is not warranted for most patients. However, patients with > or = 4 involved axillary lymph nodes, >20% involved axillary nodes, or gross extranodal extension are at increased risk of failure in the supraclavicular fossa/axillary apex and should receive radiation to undissected regions in addition to the chest wall.

Salvage treatment for local or local-regional recurrence after initial breast conservation treatment with radiation for ductal carcinoma in situ.

The present study evaluated the outcome of salvage treatment for women with local or local-regional recurrence after initial breast conservation treatment with radiation for mammographically detected ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast. The study cohort consisted of 90 women with local only first failure (n=85) or local-regional only first failure (n=5). The histology at the time of recurrence was invasive carcinoma for 53 patients (59%), non-invasive carcinoma for 34 patients (38%), angiosarcoma for one patient (1%), and unknown for two patients (2%). The median follow-up after salvage treatment was 5.5 years (mean=5.8 years; range=0.2-14.2 years). The 10-year rates of overall survival, cause-specific survival, and freedom from distant metastases after salvage treatment were 83%, 95%, and 91%, respectively. Adverse prognostic factors for the development of subsequent distant metastases after salvage treatment were invasive histology of the local recurrence and pathologically positive axillary lymph nodes. These results demonstrate that local and local-regional recurrences can be salvaged with high rates of survival and freedom from distant metastases. Close follow-up after initial breast conservation treatment with radiation is warranted for the early detection of potentially salvageable local and local-regional recurrences.

Predictors of locoregional recurrence in patients with locally advanced breast cancer treated with neoadjuvant chemotherapy, mastectomy, and radiotherapy.

PURPOSE: To identify the clinical and pathologic factors predictive of locoregional recurrence (LRR) after neoadjuvant chemotherapy, mastectomy, and radiotherapy. METHODS AND MATERIALS: We retrospectively reviewed the hospital records of 542 patients treated on six consecutive institutional prospective trials using neoadjuvant chemotherapy and postmastectomy radiotherapy. The clinical stage (American Joint Committee on Cancer, 1988) was Stage II in 17%, Stage IIIA in 30%, Stage IIIB in 43%, and Stage IV (ipsilateral supraclavicular disease) in 10%. All LRRs were considered events, irrespective of the timing to distant metastases. RESULTS: The median follow-up was 70 months. The 5-year and 10-year actuarial LRR rate was 9% and 11%, respectively. The clinical factors associated with LRR included combined clinical stage, clinical T stage, ipsilateral supraclavicular nodal disease, chemotherapy response, physical examination size after chemotherapy, and no tamoxifen use (p < or = 0.04 for all factors). The pathologic predictors of LRR included the number of positive nodes, dissection of <10 nodes, multifocal/multicentric disease, lymphovascular space invasion, extracapsular extension, skin/nipple involvement, and estrogen receptor-negative disease (p

Long-term outcome after breast-conservation treatment with radiation for mammographically detected ductal carcinoma in situ of the breast.

BACKGROUND: Ductal carcinoma in situ (DCIS) is detected most commonly on routine screening mammography in the asymptomatic patient, and has a long natural history. The objective of the current study was to determine the long-term outcome after breast-conservation surgery followed by definitive breast irradiation for women with mammographically detected DCIS of the breast. METHODS: In total, 1003 women with unilateral, mammographically detected DCIS of the breast underwent breast-conserving surgery followed by definitive breast irradiation. These women were treated in 10 institutions in North America and Europe. The median follow-up was 8.5 years (mean, 9.0 years; range, 0.2-24.6 years). RESULTS: The 15-year overall survival rate was 89%, and the 15-year cause-specific survival rate was 98%. The 15-year rate of freedom from distant metastases was 97%. In total, there were 100 local failures (10%) in the treated breast. The 15-year rate of any local failure was 19%, and the 15-year rate of local only first failure was 16%. Patient age > or = 50 years at the time of treatment and negative final pathology margins from the primary tumor excision both were associated independently with a lower risk of local failure in univariate analysis (P = 0.00062 and P = 0.024, respectively) and in multivariate analysis (P = 0.00057 and P = 0.0026, respectively). For favorable subgroups of patients age > or = 50 years or with negative resection margins, the 10-year risk of local failure was < or = 8%. CONCLUSIONS: The current results support the use of breast-conserving surgery followed by definitive breast irradiation for the treatment of patients with mammographically detected DCIS of the breast. Patient age > or = 50 years at the time of treatment and negative resection margins both were associated independently with a decreased risk of local failure.

Breast conservation after neoadjuvant chemotherapy.

BACKGROUND: The appropriate selection criteria for breast-conserving therapy (BCT) after neoadjuvant chemotherapy are poorly defined. The purpose of the current report was to develop a prognostic index to help refine selection criteria and to serve as a general framework for clinical decision-making for patients treated by this multimodality approach. METHODS: From a group of 340 patients treated with BCT after neoadjuvant chemotherapy, the authors previously determined 4 statistically significant predictors of ipsilateral breast tumor recurrence (IBTR) and locoregional recurrence (LRR): clinical N2 or N3 disease, residual pathologic tumor size > than 2 cm, a multifocal pattern of residual disease, and lymphovascular space invasion in the specimen. The M. D. Anderson Prognostic Index (MDAPI) was developed by assigning scores of 0 (favorable) or 1 (unfavorable) for each of these 4 variables and using the total to give an overall MDAPI score of 0-4. RESULTS: The MDAPI stratified the 340 patients into 3 subsets with statistically different levels of risk for IBTR and LRR after neoadjuvant chemotherapy and BCT. Actuarial 5-year IBTR-free survival rates were 97%, 88%, and 82% for patients in the low (MDAPI overall score 0 or 1, n=276), intermediate (MDAPI score 2, n=43), and high (MDAPI score 3 or 4, n=12) risk groups, respectively (P<0.001). Corresponding actuarial 5-year LRR-free survival rates were 94%, 83%, and 58%, respectively (P<0.001). CONCLUSIONS: Patients with an MDAPI score of 0 or 1, which made up 81% of the study population, had very low rates of IBTR and LRR. The MDAPI enabled the identification of a small group (4%) of patients who are at high risk for IBTR and LRR and who may benefit from alternative locoregional treatment strategies.

Postmastectomy radiation improves local-regional control and survival for selected patients with locally advanced breast cancer treated with neoadjuvant chemotherapy and mastectomy.

PURPOSE: To evaluate the efficacy of radiation in patients treated with neoadjuvant chemotherapy and mastectomy. PATIENTS AND METHODS: We retrospectively analyzed the outcomes of 542 patients treated on six consecutive institutional prospective trials with neoadjuvant chemotherapy, mastectomy, and radiation. These data were compared to those of 134 patients who received similar treatment in these same trials but without radiation. RESULTS: Irradiated patients had a lower rate of local-regional recurrence (LRR) (10-year rates: 11% v 22%, P = .0001). Radiation reduced LRR for patients with clinical T3 or T4 tumors, stage > or = IIB disease (AJCC 1988), pathological tumor size >2 cm, or four or more positive nodes (P < or = .002 for all comparisons). Patients who presented with clinically advanced stage III or IV disease but subsequently achieved a pathological complete response to neoadjuvant chemotherapy still had a high rate of LRR, which was significantly reduced with radiation (10-year rates: 33% v 3%, P = .006). Radiation improved cause-specific survival (CSS) in the following subsets: stage > or = IIIB disease, clinical T4 tumors, and four or more positive nodes (P < or = .007 for all comparisons). On multivariate analyses of LRR and CSS, the hazard ratios for lack of radiation were 4.7 (95% CI, 2.7 to 8.1; P < .0001) and 2.0 (95% CI, 1.4 to 2.9; P < .0001), respectively. CONCLUSION: After neoadjuvant chemotherapy and mastectomy, comprehensive radiation was found to benefit both local control and survival for patients presenting with clinical T3 tumors or stage III-IV (ipsilateral supraclavicular nodal) disease and for patients with four or more positive nodes. Radiation should be considered for these patients regardless of their response to initial chemotherapy.

Clinically relevant pneumonitis after sequential paclitaxel-based chemotherapy and radiotherapy in breast cancer patients.

BACKGROUND: Taxane-based chemotherapy has been associated with an increased risk of radiation pneumonitis in patients with breast cancer. To obtain additional information about this association, we investigated the association between paclitaxel chemotherapy and radiation pneumonitis in patients participating in a phase III randomized study. METHODS: Five hundred and twenty-four breast cancer patients were prospectively and randomly assigned to receive either four cycles of paclitaxel followed by four cycles of 5-fluorouracil, doxorubicin, cyclophosphamide (FAC) or eight cycles of FAC. One hundred and eighty-nine of these patients (100 in the paclitaxel-FAC group and 89 in the FAC group) subsequently underwent radiation therapy in our institution and had medical records available to review for pulmonary symptoms. In addition, a radiologist who was unaware of the type of treatment scored chest x-ray changes after radiation treatment. Crude rates of radiation pneumonitis were compared with chi-square or Fisher's exact test, and actuarial rates were assessed with Kaplan-Meier and log-rank tests. All statistical tests were two-sided. RESULTS: No difference in the rate of clinically relevant radiation pneumonitis was observed between the two groups (5.0% in the paclitaxel-FAC group versus 4.5% in the FAC group; difference = 0.5%, 95% CI = -6.6% to 5.5%; P = 1.00). Oral steroids for pneumonitis were taken by two patients in the paclitaxel-FAC group but by none in the FAC group, and no patient was hospitalized for or died of radiation pneumonitis. The paclitaxel-FAC group (39.3%) had a higher rate of radiographic changes after irradiation than the FAC group (23.7%; difference = 15.6%, 95% CI = -0.11% to 28.8%; P = .034). CONCLUSION: Patients with breast cancer treated with sequential paclitaxel, FAC, and radiation therapy appeared to have a very low rate of clinically relevant radiation pneumonitis that was no different from that of patients treated with FAC alone.

Her2/neu-positive disease does not increase risk of locoregional recurrence for patients treated with neoadjuvant doxorubicin-based chemotherapy, mastectomy, and radiotherapy.

PURPOSE: Preclinical data suggest that overexpression of Her2/neu confers cellular radioresistance. We retrospectively studied whether Her2/neu-positive disease was associated with locoregional recurrence (LRR) after postmastectomy radiotherapy (RT) for breast cancer. METHODS AND MATERIALS: Data from 337 patients treated in four institutional prospective clinical trials neoadjuvant doxorubicin-based chemotherapy, mastectomy, and RT were reviewed. The trials were conducted between 1989 and 2000. Of the 337 patients, 108 (32%) had tumors that were tested for Her2/neu, with positivity defined by 3+ immunohistochemistry staining or gene amplification detected by fluorescence in situ hybridization. RT was delivered to the chest wall and draining lymphatics (median dose, 50 Gy) followed by a chest wall boost (median dose, 10 Gy). RESULTS: Thirty-two patients had Her2/neu-positive disease and 76 patients had Her2/neu-negative disease. The Her2/neu-positive tumors were associated with a greater rate of estrogen receptor-negative disease (p = 0.03), the presence of supraclavicular disease at diagnosis (p = 0.027), and a greater number of positive lymph nodes after chemotherapy (p = 0.026). Despite these adverse features, the actuarial overall LRR rate was roughly equivalent for the patients with Her2/neu-positive tumors vs. those with Her2/neu-negative tumors (5-year rate 17.5% vs. 13.9%, respectively; 10-year rate 17.5% vs. 18.9%, respectively; p = 0.757). On Cox regression analysis of LRR adjusted for N stage and estrogen receptor status, the hazard ratio for Her2/neu positivity was 0.89 (95% confidence interval, 0.31-2.59; p = 0.83). CONCLUSION: Her2/neu overexpression does not appear to predispose to LRR after neoadjuvant doxorubicin-based chemotherapy, mastectomy, and RT.

Factors predictive of having four or more positive axillary lymph nodes in patients with positive sentinel lymph nodes: implications for selection of radiation fields.

PURPOSE: The optimal design of radiation fields for patients with positive sentinel lymph nodes (SLNs) who do not undergo axillary dissection is unknown. We have previously shown that modified breast tangent fields can include most axillary Level I-II lymph nodes. We have also reported that irradiation of the axillary apex/supraclavicular fossa is indicated for patients with four or more positive axillary lymph nodes. To determine the optimal arrangement for patients with positive SLNs, we studied what factors predicted for having four or more positive lymph nodes. METHODS AND MATERIALS: We reviewed the records of 339 consecutive patients with one to three positive SLNs who underwent complete axillary dissection at our institution between 1995 and 2002. We separately analyzed the outcome for those initially treated with surgery (n = 265) and those receiving neoadjuvant chemotherapy (n = 74). A logistic regression model was used to identify independent factors predictive for four or more positive lymph nodes. RESULTS: A total of 28 of 265 patients in the initial surgery group and 20 of 74 patients in the neoadjuvant group had four or more positive lymph nodes. In the initial surgery group, the independent factors associated with four or more positive lymph nodes were no drainage seen on lymphoscintigraphy (rate, 38%, odds ratio [OR] = 5.4, p = 0.03), more than one positive SLN (rate, 24-42%, OR = 2.9, p = 0.02), and lymphovascular space invasion (LVSI; rate, 25%, OR = 4.8, p = 0.01). Of the 106 patients without any of these factors, only 2 had four or more positive lymph nodes. For the patients treated with neoadjuvant chemotherapy, the independent factors were clinical Stage III (rate, 48%, OR = 3.1, p = 0.03), more than one positive SLN (rate, 37-67%, OR = 4.8, p = 0.03), and LVSI (rate, 62%, OR = 8.1, p = 0.02). Of the 28 patients without any of these factors, only 1 had four or more positive lymph nodes. CONCLUSION: It is reasonable to treat with modified tangents fields that include most axillary Level I-II nodes for patients with one positive SLN who do not undergo axillary dissection if drainage is seen on lymphoscintigraphy and no LVSI is present. This approach is also reasonable for patients treated with neoadjuvant chemotherapy who have Stage II disease, no LVSI, and only one positive SLN. The remaining patients have a greater risk of having four or more positive lymph nodes, and, therefore, the high axilla/supraclavicular fossa should also be included in the radiation fields.

The use of alternate, non-cross-resistant adjuvant chemotherapy on the basis of pathologic response to a neoadjuvant doxorubicin-based regimen in women with operable breast cancer: long-term results from a prospective randomized trial.

PURPOSE: To evaluate the use of an alternate, non-cross-resistant adjuvant chemotherapy regimen in women with a poor pathologic response to a preoperative doxorubicin-based regimen. PATIENTS AND METHODS: Patients with locally advanced breast cancer received three cycles of vincristine, doxorubicin, cyclophosphamide, and prednisone (VACP) every 21 days followed by surgery. Patients with less than 1 cm(3) residual tumor at mastectomy received an additional five cycles of VACP. Those with more than 1 cm(3) residual tumor were randomly assigned to receive an additional five cycles of VACP or five cycles of vinblastine, methotrexate with calcium leucovorin rescue, and fluorouracil (VbMF). RESULTS: One hundred ninety-three patients were evaluable. Overall clinical response was seen in 83.4% after three cycles of VACP, whereas the pathologic complete response was 12.2%. One hundred six patients were randomly assigned to VACP or VbMF. Those receiving VbMF achieved higher relapse-free survival (RFS) and overall survival (OS) than those who received additional VACP, although the differences did not reach statistical significance. Initial stage of tumor, clinical complete response, and pathologic complete response were all associated with statistically superior survival rates. CONCLUSION: Clinical and pathologic response to preoperative doxorubicin-based chemotherapy predicted for improved survival in women with operable breast cancer. For those with a poor response to initial neoadjuvant chemotherapy, treatment with VbMF was associated with a trend toward improved RFS and OS compared with those continuing with the doxorubicin regimen.

Breast conservation after neoadjuvant chemotherapy: the MD Anderson cancer center experience.

PURPOSE: To determine patterns of local-regional recurrence (LRR) and ipsilateral breast tumor recurrence (IBTR) among patients treated with breast conservation therapy after neoadjuvant chemotherapy. PATIENTS AND METHODS: Between 1987 and 2000, 340 cases of breast cancer were treated with neoadjuvant chemotherapy followed by conservative surgery and radiation therapy. Clinical stage at diagnosis (according to the 2003 American Joint Committee on Cancer system) was I in 4%, II in 58%, and III in 38% of patients. Only 4% had positive surgical margins. RESULTS: At a median follow-up period of 60 months (range, 10 to 180 months), 29 patients had developed LRR, 16 of which were IBTRs. Five-year actuarial rates of IBTR-free and LRR-free survival were 95% and 91%, respectively. Variables that positively correlated with IBTR and LRR were clinical N2 or N3 disease, pathologic residual tumor larger than 2 cm, a multifocal pattern of residual disease, and lymphovascular space invasion in the specimen. The presence of any one of these factors was associated with 5-year actuarial IBTR-free and LRR-free survival rates of 87% to 91% and 77% to 84%, respectively. Initial T category (T1-2 v T3-4) correlated with LRR but did not correlate with IBTR (5-year IBTR-free rates of 96% v 92%, respectively, P =.19). CONCLUSION: Breast conservation therapy after neoadjuvant chemotherapy results in acceptably low rates of LRR and IBTR in appropriately selected patients, even those with T3 or T4 disease. Advanced nodal involvement at diagnosis, residual tumor larger than 2 cm, multifocal residual disease, and lymphovascular space invasion predict higher rates of LRR and IBTR.

Delayed-immediate breast reconstruction.

In patients with early-stage breast cancer who are scheduled to undergo mastectomy and desire breast reconstruction, the optimal timing of reconstruction depends on whether postmastectomy radiation therapy will be needed. Immediate reconstruction offers the best aesthetic outcomes if postmastectomy radiation therapy is not needed, but if postmastectomy radiation therapy is required, delayed reconstruction is preferable to avoid potential aesthetic and radiation-delivery problems. Unfortunately, the need for postmastectomy radiation therapy cannot be reliably determined until review of the permanent tissue sections. The authors recently implemented a two-stage approach, delayed-immediate breast reconstruction, to optimize reconstruction in patients at risk for requiring postmastectomy radiation therapy when the need for postmastectomy radiation therapy is not known at the time of mastectomy. Stage 1 consists of skin-sparing mastectomy with insertion of a completely filled textured saline tissue expander. After review of permanent sections, patients who did not require post-mastectomy radiation therapy underwent immediate reconstruction (stage 2) and patients who required postmastectomy radiation therapy completed postmastectomy radiation therapy and then underwent standard delayed reconstruction. In this study, the feasibility and outcomes of this approach were reviewed. Fourteen patients were treated with delayed-immediate reconstruction between May of 2002 and June of 2003. Twelve patients had unilateral reconstruction and two patients had bilateral reconstruction, for a total of 16 treated breasts. All patients completed stage 1. Tissue expanders were inserted subpectorally in 15 breasts and subcutaneously in one breast. The mean intraoperative expander fill volume was 475 cc (range, 250 to 750 cc). Three patients required postmastectomy radiation therapy and underwent delayed reconstruction. Eleven patients did not require postmastectomy radiation therapy. Nine patients had 11 breast reconstructions (stage 2), six with free transverse rectus abdominis musculocutaneous (TRAM) flaps, one with a superior gluteal artery perforator flap, and four with a latissimus dorsi flap plus an implant. The median interval between stages was 13 days (range, 11 to 22 days). Two patients who did not require postmastectomy radiation therapy have not yet had stage 2 reconstruction, one because she wished to delay reconstruction and the other because she required additional tissue expansion before permanent implant placement. Six complications occurred. The stage 1 complications involved two cases of mastectomy skin necrosis in patients who required post-mastectomy radiation therapy; one patient required removal of the subcutaneously placed expander before postmastectomy radiation therapy and the other patient had a subpectorally placed expander that only required local wound care. The stage 2 complications were a recipient-site seroma in a patient with a latissimus dorsi flap, a recipient-site hematoma in the patient with the superior gluteal artery perforator flap, and two arterial thromboses in patients with TRAM flaps. Both TRAM flaps were salvaged. Delayed-immediate reconstruction is technically feasible and safe in patients with early-stage breast cancer who may require postmastectomy radiation therapy. With this approach, patients who do not require postmastectomy radiation therapy can achieve aesthetic outcomes essentially the same as those with immediate reconstruction, and patients who require postmastectomy radiation therapy can avoid the aesthetic and radiation-delivery problems that can occur after an immediate breast reconstruction.

T3 disease at presentation or pathologic involvement of four or more lymph nodes predict for locoregional recurrence in stage II breast cancer treated with neoadjuvant chemotherapy and mastectomy without radiotherapy.

PURPOSE: To help define the clinical and pathologic predictors of locoregional recurrence (LRR) in breast cancer patients treated with neoadjuvant chemotherapy and mastectomy without radiotherapy for early-stage disease. METHODS AND MATERIALS: We retrospectively reviewed the outcomes of all 132 patients with Stage I or II breast cancer treated in prospective institutional trials with neoadjuvant chemotherapy and mastectomy without radiotherapy between 1974 and 2001. The clinical stage (American Joint Committee on Cancer 1988) at diagnosis was I in 5%, IIA in 46%, and IIB in 49% of patients. The median age at diagnosis was 49 years. All patients were treated with either a doxorubicin-based neoadjuvant regimen or single-agent paclitaxel. The total LRR rates were calculated by the Kaplan-Meier method, and comparisons were made with two-sided log-rank tests. The median follow-up was 46 months. RESULTS: The actuarial LRR rate at both 5 and 10 years was 10%. Factors that correlated positively with LRR included clinical Stage T3N0 (p = 0.0057), four or more positive lymph nodes at surgery (p = 0.0001), age < or =40 years at diagnosis (p = 0.0001), and no use of tamoxifen. In the patients who did not receive tamoxifen, estrogen receptor-positive disease correlated positively with LRR (p = 0.0067). The 5-year LRR rate for the 42 patients with clinical Stage T1 or T2 disease and one to three positive lymph nodes at surgery was 5% (only two events). CONCLUSIONS: For patients with clinical Stage II breast cancer, T3 primary disease, four or more positive lymph nodes after chemotherapy, and age < or =40 years old predicted for LRR. For most patients with clinical T1 or T2 disease and one to three positive lymph nodes, the 5-year risk for LRR was low, and the routine inclusion of postmastectomy radiotherapy does not appear to be justified.

A Ser49Cys variant in the ataxia telangiectasia, mutated, gene that is more common in patients with breast carcinoma compared with population controls.

BACKGROUND: Mothers of children who have ataxia telangiectasia have been reported to be at increased risk for development of breast carcinoma. To test whether sequence variants in the ataxia telangiectasia, mutated, gene (ATM) are associated with breast carcinoma, the authors compared the frequency of ATM cDNA sequence changes in patients with breast carcinoma with the corresponding frequency in control patients. METHODS: The authors sequenced ATM cDNA from 91 patients with breast carcinoma and compared the frequencies of sequence changes in these patients with the corresponding frequencies in a control sample of 940 individuals with no history of malignant disease. RESULTS: Thirty-five patients with breast carcinoma had one or more single-base changes in ATM. Three genetic variants were found in at least two patients. These variants resulted in Asp1853Asn, Pro1054Arg, or Ser49Cys amino acid substitutions in the ATM protein. The Ser49Cys variant was more common in patients with breast carcinoma than in the control patients, with respective frequencies of 6.7% (5 of 75 patients) and 1.3% (12 of 940 patients; P=0.006; Fisher two-sided exact test). The subgroup of patients with bilateral breast carcinoma had a Ser49Cys frequency of 11.8% (2 of 17 patients), which again was significantly different from what was observed in the control group (P=0.024; Fisher two-sided exact test). The allele frequencies of the other two variants were not different between case patients and control patients. CONCLUSIONS: Patients with breast carcinoma, particularly those with bilateral disease, were more likely to have a variant in the ATM gene that resulted in a Ser49Cys substitution in the gene product. Additional studies are needed to evaluate the potential functional consequences of the Ser49Cys substitution and confirm the relevance of this variant in the development of breast carcinoma.

Advances in radiation treatments of breast cancer.

During the past decade, improvements in treatment-planning tools, computer and imaging technologies, and new therapeutic modalities have allowed radiation to be delivered in a conformal fashion while minimizing treatment toxicity. It is important that physicians involved in breast cancer treatment recognize the numerous advances that have occurred in the delivery of radiation therapy. Changes in 3 specific areas in treatment planning and delivery have revolutionized the way we approach breast cancer treatment: the design of radiation fields using computed tomography (CT) data sets, the development of 3-dimensional dose-calculation algorithms, and the development of new methods to modulate the delivery of radiation dose. With the advent of CT simulators, individual patient anatomy and pathology can be readily visualized and reconstructed in axial, coronal, and sagittal views. With an improved anatomic delineation between the target volumes and critical organ structures, the treatment fields can be designed to be more congruous to the areas at highest risk. In the past few years, new 3-dimensional dose-calculation algorithms have been generated that more accurately calculate dose distributions throughout the treatment-planning volume. Finally, modern linear accelerators allow for modulation of the dose intensity of the radiation beam, which may lead to improved aesthetics and decreased side effects while ensuring that the volumes at high risk receive the prescribed dose. Radiation therapy can be delivered safely and effectively to patients with breast cancer.