Locally advanced breast cancer. American College of Radiology. ACR Appropriateness Criteria.
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Publications and source records attributed to M D McNeese.
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PURPOSE: Hyperfractionated, accelerated radiotherapy (HART) has been advocated for patients with local-regionally recurrent breast cancer because it is believed to enhance treatment effects in rapidly proliferating or chemoresistant tumors. This report examines the value of HART in patients with local-regionally recurrent breast cancer treated with multimodality therapy. METHODS AND MATERIALS: The study included 148 patients with local-regionally recurrent breast cancer after mastectomy, who were treated with definitive local irradiation and systemic therapy consisting of either tamoxifen, cytotoxic chemotherapy, or both, along with excision of the recurrent tumor when possible. Patients with distant metastases were excluded, except for two patients with ipsilateral supraclavicular nodal metastases. Patients received comprehensive irradiation to the chest wall and regional lymphatics to a median dose of 45 Gy, with a boost to 60 Gy to areas of recurrence. Sixty-eight patients (46%) were treated once daily at 2 Gy/fraction (fx), and 80 (54%) were treated twice daily at 1.5 Gy/fx. Forty-eight patients (32%), who had palpable gross disease that was unresponsive to systemic therapy and/or unresectable, were irradiated. The median follow-up time of surviving patients was 78 months. RESULTS: Overall actuarial local-regional control (LRC) rates at 5 and 10 years were 68% and 55%, respectively. Five- and ten-year actuarial overall survival (OS) and disease-free survival (DFS) rates were 50% and 35%, 39% and 29%, respectively. Univariate analysis revealed that LRC was adversely affected by 1. advanced initial American Joint Committee on Cancer (AJCC) stage (p = 0.001), 2. clinically evident residual disease at time of treatment (p < 0.0001), 3. more than three positive nodes at initial mastectomy (p = 0.014), 4. short interval from mastectomy to recurrence (< 24 months, p = 0.0007), 5. nuclear grade (III vs. I or II, p = 0.045), and 6. number of recurrent nodules (1 vs. > 1, p = 0.02). Patient age at time of recurrence (< 40 vs. > or = 40 years), recurrence location on the chest wall, estrogen receptor status, progesterone receptor status or menopausal status did not adversely affect LRC. On multivariate analysis, only clinically evident residual disease at the time of treatment and short interval from mastectomy to recurrence remained significant. When once-a-day irradiation was compared to the twice-a-day schedule, no significant differences were seen in LRC (67% vs. 68%), OS (47% vs. 52%), or DFS (42% vs. 36%) for the entire group of patients at 5 years. Pairwise comparison of the two fractionation schedules in each of the adverse outcome subgroups identified above showed no clinically significant differences in LRC at 5 years. For the 48 patients who began radiotherapy with measurable gross local recurrence, the complete response rate to radiotherapy was 73%, with no difference seen between the two fractionation schedules. The incidence of acute and chronic radiation-related complications was similar in both treatment groups. CONCLUSIONS: Hyperfractionated accelerated radiotherapy, although well tolerated by patients with local-regionally recurrent breast cancer, did not result in superior local-regional control rates when compared to daily fractionated regimens. Alternative strategies, such as dose escalation or chemoradiation, may be required to improve control.
The genetic determinants for most breast cancer cases remain elusive. However, a mutation in a tumor suppressor gene, such as p53, BRCA1, BRCA2, or ATM, has been determined to be one mechanism of breast carcinogenesis. It has been established that inherited mutations in p53, BRCA1, and BRCA2 significantly contribute to breast cancer risk, although the importance of an inherited ATM mutation is controversial. Sporadic mutations in p53 are also common in breast cancer cells. The precise deficiencies that result from these genetic mutations have yet to be fully described. Although the functions of these genes are different, they are all involved in the maintenance of genomic stability after DNA damage. Mutations that impair the function of these four genes may adversely affect the manner in which DNA damage is processed. It is likely that the risk of breast cancer development is increased through this mechanism. In this article, we review the relevancy of p53, BRCA1, BRCA2, and ATM mutations to breast cancer development, and review the in vitro, in vivo, and clinical data exploring the mechanisms by which these mutations affect genomic integrity and DNA damage repair.
The goal of postmastectomy irradiation is to eliminate residual viable tumor in tissue remaining after standard mastectomy. Because this subclinical disease is, by definition, not detectable by current technology, the choice of patients and treatment volumes for postmastectomy irradiation must be inferred from a variety of data sources. The absolute risk of locoregional recurrence is related to the stage of disease, the extent of lymphatic involvement, and other treatment received. Patterns of failure analyses consistently identify the chest wall as the most important target for treatment with radiation therapy in high-risk patients. When patients with multiple locoregional sites of recurrence are included, the chest wall may be involved in as many as 60% to 80% of patients. The second most common place for locoregional failure is the undissected lymphatics of the paraclavicular region. The cumulative probability of failure in this region ranges from 10% to 35% of the patients treated for locoregional recurrence. Microscopic tumor metastases in the internal mammary chain are theorized to represent a potential source for distant metastases. Each of the prospective trials of postmastectomy irradiation that have shown survival benefit included the internal mammary chain within their target volume. Nonetheless, local failure in the internal mammary nodes is an uncommon finding. Similarly, after a level I and II axillary dissection, axillary failure is a minor component of local recurrence risk, and it is probable that only a subset of patients may benefit from axillary irradiation.
Some patients with certain preexisting health conditions may be at elevated risk for unusually intense radiation-induced skin reactions and late tissue damage from high-dose interventional procedures. The authors present a case report of a patient with mixed connective tissue disease and non-insulin-dependent diabetes mellitus who developed an unusual complication after placement of a transjugular intrahepatic portosystemic shunt. On the basis of a review of the literature, the following experiences may help identify patients at increased risk: previous high-dose procedures, connective tissue disease, diabetes mellitus, and homozygosity for ataxia telangiectasia.
PURPOSE: To assess patient and tumor characteristics associated with a complete pathologic response (pCR) in both the breast and axillary lymph node specimens and the outcome of patients found to have a pCR after neoadjuvant chemotherapy for locally advanced breast cancer (LABC). PATIENTS AND METHODS: Three hundred seventy-two LABC patients received treatment in two prospective neoadjuvant trials using four cycles of doxorubicin-containing chemotherapy. Patients had a total mastectomy with axillary dissection or segmental mastectomy and axillary dissection followed by four or more cycles of additional chemotherapy. Patients then received irradiation treatment of the chest-wall or breast and regional lymphatics. Median follow-up was 58 months (range, 8 to 99 months). RESULTS: The initial nodal status, age, and stage distribution of patients with a pCR were not significantly different from those of patients with less than a pCR (P>.05). Patients with a pCR had initial tumors that were more likely to be estrogen receptor (ER)-negative (P<.01), and anaplastic (P = .01) but of smaller size (P<.01) than those of patients with less than a pCR. Upon multivariate analysis, the effects of ER status and nuclear grade were independent of initial tumor size. Sixteen percent of the patients in this study (n = 60) had a pathologic complete primary tumor response. Twelve percent of patients (n = 43) had no microscopic evidence of invasive cancer in their breast and axillary specimens. A pathologic complete primary tumor response was predictive of a complete axillary lymph node response (P<.01 ). The 5-year overall and disease-free survival rates were significantly higher in the group who had a pCR (89% and 87%, respectively) than in the group who had less than a pCR (64% and 58%, respectively; P<.01). CONCLUSION: Neoadjuvant chemotherapy has the capacity to completely clear the breast and axillary lymph nodes of invasive tumor before surgery. Patients with LABC who have a pCR in the breast and axillary nodes have a significantly improved disease-free survival rate. However, a pCR does not entirely eliminate recurrence. Further efforts should focus on elucidating the molecular mechanisms associated with this response.
The purpose of this paper is to determine whether using off-axis isoseparation curves to optimize the collimator rotation angle improves dose homogeneity. Eleven intact breast irradiation patients underwent computerized tomography (CT) treatment planning with 1 cm abutting slices. Central plane treatment planning, using 6 MV photons, tissue inhomogeneity corrections, and isocentric opposed tangent treatment fields, was performed. Collimators were rotated to match chest wall slope through the use of a beam's-eye-view setting. Patient separations were measured from the apex of the breast to the posterior field border on each axial CT slice. Sagittal-plane isoseparation curves were constructed from these measurements. Using these curves, the collimator rotation that minimized off-axis separation differences was determined. A comparison of off-axis dose inhomogeneity was performed for patients with a > or =10 degrees difference between this optimized collimator angle and the angle determined by chest wall slope. These comparative treatment plans differed only with respect to collimator angle rotation. The mean optimal collimator rotation angle differed significantly from the mean rotation angle which matched the chest wall slope (5.4 degrees vs. 11 degrees, respectively, P < 0.001). Four of the 11 patients had rotation angle differences of 10 degrees. In these patients, the optimization of collimator angle reduced the percentage of breast volume to "that" received > or =110% of the prescribed dose. For the patient with the largest breast size to the patient with the smallest breast size the decreases were, respectively, 5% (15% to 10%), 3% (24% to 21%), 1% (4% to 3%), and 1% (0.9% to 0%). The mean reduction in dose inhomogeneity was greatest in the inferior breast quadrants. At 6 cm and 4 cm off axis, the mean reductions in the percentages of the breast tissue to "that" received 110% of the prescribed dose were respectively 15.1% and 5.3 %. Optimizing the collimator angle through the use of isoseparation curves decreases dose inhomogeneity. The greatest improvements are in the inferior quadrants of the intact breast. The improved dose homogeneity may have clinical relevance in the treatment of patients with large breast sizes.
Our purpose was to examine the role of radiotherapy in the management of phyllodes tumor of the breast. Eight patients were treated with adjuvant radiotherapy for nonmetastatic phyllodes tumor of the breast at the M.D. Anderson Cancer Center between December 1988-August 1993. Tumors were classified as benign (n=2), borderline (indeterminate; n=1), or malignant (n=5). Median follow-up was 36.5 months. Primary surgery consisted of either lumpectomy in 2 patients or mastectomy in 6 patients. Seven patients received adjuvant radiation therapy to the breast or chest wall to a dose of 60 Gy. One patient received 50 Gy to the breast, followed by an interstitial boost of 20 Gy for a total of 70 Gy. Radiotherapy was administered for a combination of reasons, including bulky tumor volume, positive margins, recurrence, and/or malignant histology. There were no local or distant failures. This retrospective review suggests that adjuvant radiotherapy may be underutilized in the treatment of phyllodes tumor of the breast, particularly in patients with adverse features. Although treatment to the breast or chest wall (not the lymphatics) to a dose of 60 Gy appears effective, a dose-response has not been established, and lower doses (50-60 Gy) may be equally effective.
Segmental resection and radiotherapy is an accepted alternative over mastectomy for small, staged breast malignancies. However, women with large, pendulous breasts have been documented to have poorer cosmetic outcomes when undergoing irradiation after breast conservative surgery compared with women with small- or medium-size breasts, thought to be caused by dose inhomogeneity. The purpose of this study was to evaluate the efficacy of combining reduction mammaplasty with breast conservative surgery to facilitate postoperative irradiation. Between 1988 and 1996, 10 women have undergone bilateral reduction mammaplasty for breast malignancy followed by radiation therapy at our center. All women wished to avoid mastectomy (average age, 59 years). All lesions were detected preoperatively on mammography. The average amount of tissue removed was 945 g per breast. A variety of reduction techniques were employed to include the malignant lesions. All patients received 50 Gy of radiation therapy delivered in 25 fractions following reduction mammaplasty during a 5-week period. Radiation therapy was usually initiated within 4 weeks following surgery. Follow-up is currently 37 months, with all patients being followed for at least 8 months. No patients have had complications from the surgery or radiation therapy. No local recurrent malignancies have been detected. Cosmesis has been good to excellent in all patients. Despite equivalent survival outcomes for mastectomy for early-stage breast cancer, certain women are not good candidates for breast conservation and radiation therapy. An alternative for women with large, pendulous breasts that combines breast conservation therapy and concurrent bilateral reduction mammaplasty should be considered. This combination, in selected women, provides good functional and cosmetic results, and at the same time minimizes the potential difficulties of radiation therapy.
BACKGROUND: Controversy exists as to the treatment regimen necessary to best provide optimal local control for inflammatory breast carcinoma (IBC). This study was conducted to determine if mastectomy combined with radiotherapy offered any advantages over radiotherapy alone in patients with IBC who had been treated with doxorubicin-based combination chemotherapy. METHODS: A retrospective review of 178 women treated for IBC on doxorubicin-based multimodality therapy protocols between January 1974 and September 1993 was performed. Clinical and histologic response to treatment, time to local recurrence, survival, and ultimate control of local disease were analyzed. Kaplan-Meier analysis was used to examine survival and relapse times, and Fisher's exact test was used to test differences in treatment outcomes. Significance was determined at p < or = 0.05. RESULTS: Median follow-up was 89 months (range 22 to 223 months). Locoregional disease persisted in seven patients and recurred in 44 patients who had been rendered disease free at a median time of 10 months. The mortality rate after a local recurrence (LR) was 98%, and all patients but one with LR developed systemic metastases. Response to induction chemotherapy influenced the incidence of LR, and the amount of residual disease found on histologic examination of mastectomy specimens was highly prognostic for local failure. Patients who underwent mastectomy in addition to radiotherapy had a lower incidence of LR than did patients who received radiotherapy alone (16.3% vs. 35.7%, p = 0.015). CONCLUSIONS: The addition of mastectomy to combination chemotherapy plus radiotherapy improved local control in patients with IBC. The addition of mastectomy to chemotherapy plus radiotherapy improved distant disease-free and overall survival in patients with a clinical complete or partial response to induction chemotherapy. Patients who had no significant response to induction chemotherapy received no survival or local disease-control benefit from the addition of mastectomy to their treatment regimen. These patients should be considered for entry into clinical trials of new treatment regimens.
BACKGROUND: The relationship between an extensive intraductal component (EIC) and recurrence and survival in patients with stage I or II breast cancer treated with breast conservation therapy has not been clearly defined. METHODS: 133 patients with stage I or II breast cancer who underwent breast conservation therapy between 1978 and 1990 at The University of Texas M. D. Anderson Cancer Center were retrospectively studied. All pathology slides were reviewed to determine tumor size, nuclear grade, extent of intraductal component, number of positive lymph nodes, and histologic margins. EIC was defined as ductal carcinoma in situ (DCIS) occupying 25% or more of the area encompassed by the infiltrating tumor and DCIS present in grossly normal adjacent breast tissue. RESULTS: 110 patients are alive, and 23 have died, with a median follow-up of 7 years; 85 of 133 patients had an intraductal component, but only 18 had an EIC. Locoregional control and disease-free and overall survival were not adversely affected by the presence of an EIC. Five of 133 patients had a locoregional recurrence, but only one had an EIC. CONCLUSIONS: EIC, if negative margins can be achieved, does not adversely affect disease-free or overall survival or local control rates.
PURPOSE: To review the 20 years of experience at M. D. Anderson Cancer Center with a combined-modality approach against inflammatory breast carcinoma. PATIENTS AND METHODS: A total of 178 patients with inflammatory breast carcinoma were treated in the past 20 years at M. D. Anderson Cancer Center by a combined-modality approach under four different protocols. Each protocol included induction chemotherapy, then local therapy (radiotherapy or mastectomy), then adjuvant chemotherapy, and, if mastectomy was performed, adjuvant radiotherapy. Chemotherapy consisted of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) with or without vincristine and prednisone (VP). In protocol D, patients received an alternate adjuvant chemotherapy regimen, methotrexate and vinblastine (MV), if they did not have a complete response (CR) to induction chemotherapy. RESULTS: The median follow-up of live patients in group A was 215 months, in group B 186 months, in group C 116 months, and in group D 45 months. An estimated 28% of patients were currently free of disease beyond 15 years. At the time of analysis, 50 patients were alive without any evidence of disease. A further 12 patients died of intercurrent illness, and 15 patients were followed beyond 10 years without recurrence of disease. Among initial recurrence, 20% of patients had local failure, 39% systemic failure, and 9% CNS recurrence. Initial response to induction chemotherapy was an important prognostic factor. Disease-free survival (DFS) at 15 years was 44% in patients who had a CR to induction chemotherapy, 31% in those who had a partial response (PR), and 7% in those who had less than a PR. There was no improvement in overall survival (OS) or DFS among patients who underwent alternate chemotherapy (MV) compared with those who did not. Using surgery and radiotherapy as opposed to radiotherapy alone as local therapy did not have an impact on the DFS or OS rate. CONCLUSION: These long-term follow-up data show that with a combined-modality approach a significant fraction of patients (28%) remained free of disease beyond 15 years. In contrast, single-modality treatments yielded a DFS of less than 5%. Thus, using combined-modality treatment (chemotherapy, then mastectomy, then chemotherapy and radiotherapy) is recommended as a standard of care for inflammatory breast carcinoma.
BACKGROUND: An association between systemic scleroderma, radiation, and breast cancer has been recognized. However, localized scleroderma in the radiation port of breast cancer patients has been rarely described. OBJECTIVE: Our purpose was to describe the concurrence of localized scleroderma, supervoltage radiation, and breast carcinoma. METHODS: Patients were prospectively evaluated in a tertiary care cancer center, and the literature was reviewed. RESULTS: We describe six patients with breast cancer in whom localized scleroderma developed within their radiation port. CONCLUSION: Radiation port localized scleroderma can be a sequela of supervoltage radiation therapy in patients with breast cancer. Recognition is important because localized scleroderma can clinically mimic recurrent breast carcinoma.
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Forty-nine women with ductal carcinoma in situ (DCIS) treated with lumpectomy and irradiation were studied retrospectively. The median age was 50 years (range, 29 to 73 years) and the median follow-up time from initiation of therapy was 86 months (range, 17 to 230 months). Twelve patients presented with palpable masses (0.4 to 4 cm), three with breast thickening, and three with nipple discharge. In 31 patients the tumors were detected by mammography. Intraoperatively, excision of lesions was confirmed by specimen x-ray (38 specimens) or gross inspection (five specimens) and was recorded to be complete. No record was available in the other six patients. Margins of excision free of DCIS were microscopically confirmed in 25 specimens. The size of impalpable DCIS lesions recorded in 25 patients ranged from 0.4 to 5.0 cm (mean, 1.5 cm). Using Lagios' classification system, there were 18 classic comedocarcinomas, high nuclear grade (NG) with necrosis; seven cribriform/papillary, high NG with necrosis; 17 cribriform/micropapillary, intermediate NG with or without necrosis; and seven cribriform/micropapillary, low NG without necrosis. In two patients residual malignant calcifications were present on the postoperative mammogram. Disease recurred in the treated breast at the site of incision in five patients at 18 months and 8, 11, and 12 (two patients) years from initial therapy. The rate of local disease recurrence was 2% at 5 years and 6% at 10 years; three recurrences showed invasive ductal carcinoma and two were DCIS. To evaluate risk factors the following characteristics were considered: necrosis, NG, histological type, periductal fibrosis, periductal lymphoid infiltrate, margin status, age, and method of tumor detection. The end points chosen were recurrence and death from any cause (because only one patient died of disease). Although the recurrences were attributed to residual disease in two patients, of the clinical and pathological parameters evaluated, only periductal fibrosis showed a significant relationship with outcome, with a P value < or = .05 by the Wilcoxon test. On the other hand, using the proportional hazards model, necrosis was a significant predictor for recurrence (P = .02), as was the pair fibrosis and tumor detection when taken together (P = .05). Fibrosis significantly associated with high NG, Lagios' histological subtypes I and II, periductal lymphoid infiltrate, and necrosis (P < or = .0006).(ABSTRACT TRUNCATED AT 400 WORDS)
To determine whether preoperative chemotherapy sufficiently downstages disease in patients with locally advanced breast cancer to allow breast-conservation surgery, the clinical, mammographic, and histologic responses were analyzed after three cycles of preoperative vincristine, doxorubicin, cyclophosphamide, and prednisone that were administered to 143 patients with 1988 American Joint Committee on Cancer Stage IIB (17%), IIIA (36%), or IIIB (41%) disease or positive supraclavicular lymph nodes (6%) who had a complete (16%) or partial (84%) clinical response and underwent total mastectomy and axillary node dissection. Thirty-three (23%) were potential breast-conservation candidates based on criteria of complete resolution of skin edema, residual tumor size less than 5 cm, and absence of known tumor multicentricity or extensive intramammary lymphatic invasion. Of these 33, the initial tumor size decreased from a median of 5 cm to less than 1 cm, with 42% having no residual tumor in the mastectomy specimen and 45% having negative nodes. No tumor was found in any other quadrant of the breast, and no patient had a recurrence in the chest wall. After a median follow-up of 34 months, only three patients had distant metastases; two of these died of disease.