Annals of Surgical Oncology Sign the Guestbook
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mirza, N. Q.
Right arrow Articles by Hunt, K. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mirza, N. Q.
Right arrow Articles by Hunt, K. K.
Related Collections
Right arrow Sentinel lymph node
Annals of Surgical Oncology 9:256-265 (2002)
© 2002 Society of Surgical Oncology

ORIGINAL ARTICLES

Predictors of Locoregional Recurrence Among Patients With Early-Stage Breast Cancer Treated With Breast-Conserving Therapy

Nadeem Q. Mirza, MD, MPH, Georges Vlastos, MD, Funda Meric, MD, Thomas A. Buchholz, MD, Nestor Esnaola, MD, MPH, S. Eva Singletary, MD, Henry M. Kuerer, MD, PhD, Lisa A. Newman, MD, Frederick C. Ames, MD, Merrick I. Ross, MD, Barry W. Feig, MD, Raphael E. Pollock, MD, PhD, Marsha McNeese, MD, Eric Strom, MD and Kelly K. Hunt, MD

From the Departments of Surgical Oncology (NQM, GV, FM, NE, SES, HMK, LAN, FCA, MIR, BWF, REP, KKH) and Radiation Oncology (TAB, MM, ES), The University of Texas M. D. Anderson Cancer Center, Houston, Texas.

Correspondence: Address correspondence and reprint requests to: Kelly K. Hunt, MD, Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Box 444, Houston TX 77030; Fax: 713-792-4689; E-mail: khunt{at}manderson.org


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Background: Our aim was to identify predictors of locoregional recurrence (LRR) in patients with early-stage breast cancer treated with breast-conserving therapy (BCT) and long-term follow-up.

Methods: From 1970 to 1994, 1153 patients with stage I to II breast cancer underwent BCT and radiotherapy at our institution. Patients with prior breast cancer or other primary malignancies were excluded. Clinical and pathologic characteristics evaluated were age, race, tumor size, stage, pathologic tumor margins, axillary nodal involvement, estrogen and progesterone receptor status, Black’s nuclear grade, type of surgery, and use of adjuvant therapy.

Results: Of 1083 patients, 54% presented with stage I disease and 46% with stage II disease. Median age was 50 years, and median follow-up was 9 years. Axillary nodes were positive in 31% of the patients who underwent axillary dissection. LRR developed in 6%, LRR followed by systemic recurrence in 5%, and systemic recurrence alone in 13%; 76% had no evidence of recurrence at last follow-up. Age, tumor size, positive lymph nodes, and not receiving chemotherapy or hormonal therapy were independent predictors of LRR. Disease-specific survival among patients with LRR was similar to that among patients with no recurrence.

Conclusions: Multidisciplinary treatment strategies should be used to accomplish durable locoregional control after BCT.

Key Words: Breast neoplasms • Local recurrence • Predictors • Breast-conserving therapy • Survival


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Conservative treatment of early-stage breast carcinoma with lumpectomy and radiotherapy has been used1 since the 1960s and is now accepted as an alternative to mastectomy.2 An estimated 192,200 new cases of female breast cancer will be diagnosed in the United States3 in 2001, of which 75% to 80% will be stage I or II disease. Both retrospective studies4–7 and prospective randomized trials8–12 have demonstrated that breast-conserving therapy (BCT) produces rates of survival and locoregional control similar to those of mastectomy for patients with invasive breast carcinoma. Local recurrence rates from 5% to 20% have been reported in several studies of patients treated with BCT.9,13–17 However, the development of local recurrence in the breast treated with BCT nullifies the aim of cosmesis and is psychologically devastating for the patient, because these recurrences are treated by salvage mastectomy.18 The risk factors for local recurrence among patients treated with BCT have not been fully established.19 Several studies have reported that young age,7,19–22 large tumors,23 multiple tumors,24,25 positive tumor margins, 20 axillary lymph node involvement, 23 extranodal extension,23 extensive ductal carcinoma-in-situ,20,21,24,26,27 and high nuclear grade24,28 are risk factors for local recurrence. The ability to identify patients at high risk for locoregional recurrence (LRR) would help to establish specific treatment strategies for such patients.

Since the early 1970s, The University of Texas M. D. Anderson Cancer Center has routinely used BCT to treat selected patients. In this study, we reviewed the records of consecutive patients with stage I and II breast cancer who underwent lumpectomy followed by adjuvant radiotherapy. Our aim was to identify patterns of recurrence and factors predictive of LRR among these patients.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Patients
From May 1970 to December 1994, 1153 consecutive female patients with stage I and II breast cancer were treated with BCT followed by radiotherapy at the M. D. Anderson Cancer Center, and information on their cases was entered in a database. A retrospective review of this database identified patients with LRR alone, LRR followed by systemic recurrence (LRR+SR), systemic recurrence (SR) alone, or no recurrence. The medical records were then examined for additional information on clinical and pathologic variables and disease recurrence for these patients.

Patients were excluded if they had a history of invasive breast carcinoma (n = 40) or other primary malignancy (except basal cell carcinoma or carcinoma in situ of the cervix; n = 30). The following clinical and pathologic variables were assessed: age, race, tumor size, lymph node status, stage of disease, estrogen and progesterone receptor status, Black’s nuclear grade, tumor margin status, radiation boost, adjuvant chemotherapy or hormonal therapy, contralateral breast carcinoma, and LRR and distant recurrence.

Treatment
Surgical Treatment
Patients were treated with wide excision of the tumor with or without a level I or II axillary lymph node dissection (ALND). All patients had macroscopically complete excision of the primary tumor. Our re-excision policy for tumors with positive or unknown margins at pathologic examination led to 39% of the patients undergoing re-excision at our institution in an attempt to obtain negative microscopic margins.

Radiotherapy
The ipsilateral breast was treated with 45 to 50 Gy, delivered in 25 fractions over a 5-week period. Radiation was delivered in medial and lateral tangential fields of cobalt 60 (6- or 18-MV photons). A 10- to 20-Gy boost was delivered to the tumor bed by using reduced fields of electrons or interstitial implants when the re-excision specimen showed residual tumor, lymphovascular invasion, poor differentiation, or margins that were <5 mm or not specified.29

Systemic Therapy
Doxorubicin-based adjuvant chemotherapy was considered for patients with histologically proven lymph node involvement.30 Tamoxifen was considered for postmenopausal patients with estrogen receptor-positive tumors at the completion of chemotherapy or after surgery in those patients who did not receive chemotherapy.

Pathology Evaluations
Tumor histological features were obtained from the original pathology reports. All cases in which primary surgical procedures took place at outside facilities were reviewed at M. D. Anderson.

Recurrence
Medical records were reviewed for all patients coded in our BCT database as having had LRR, SR, or no recurrence. For most patients, information was obtained from the follow-up clinic notes and pathology reports; however, only the clinic notes were available for the few patients who were observed for local recurrence at an outside facility. Local recurrence was defined as any recurrent tumor developing in the ipsilateral breast. Regional recurrence was defined as evidence of recurrent tumor in the regional nodal basins.

Statistical Analysis
Descriptive statistics were used to assess frequency distributions among the groups. Categorical variables and continuous variables between groups were analyzed by {chi}2 tests and Kruskal-Wallis H tests. Disease-specific survival was defined as the interval between initial diagnosis and last follow-up, and LRR-free survival was defined as the interval between initial diagnosis and LRR. Patients who were alive or who died of a cause other than breast cancer were censored for analysis of disease-specific survival, and patients who were alive and free of breast cancer were censored for analysis of LRR-free survival. Disease-specific and LRR-free interval probabilities were calculated by the product-limit method of Kaplan and Meier, and survival rates were compared by using log-rank tests.31

For multivariate analysis, a stepwise forward logistical regression method was used to identify independent predictors of LRR. The following characteristics were categorized before entry into the model: age (<=50 vs. >50 years), race (white vs. nonwhite), tumor size (<=1.5 vs. >1.5 cm), type of surgery (lumpectomy vs. lumpectomy plus ALND), tumor margins (negative vs. positive), radiation boost (delivered vs. not delivered), chemotherapy (given vs. not given), and hormonal therapy (given vs. not given). The median values for age and tumor size of our study population were used as a cutoff.

A P value of .05 or less was considered to be statistically significant. The SPSSTM 10.07 software package (SPSS Inc., Chicago, IL) was used for statistical analysis.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 CONCLUSIONS
 REFERENCES
 
Patient and Treatment Characteristics
The initial study population comprised 1083 patients, all of whom underwent lumpectomy of the primary tumor followed by adjuvant radiotherapy. Three patients presented with bilateral breast carcinomas. Sixty-nine patients (6%) developed LRR, 56 (5%) developed LRR+SR, 136 (13%) developed SR only, and 822 (76%) had no evidence of disease recurrence at last follow-up. Because our aim was to identify predictors of LRR, patients with SR only were excluded from further analysis. Thus, the final study population consisted of 947 patients.

Demographic and treatment characteristics of these patients are listed in Table 1. The median age at diagnosis of the group as a whole was 50 years (range, 24–86 years), but patients with LRR were younger than patients with no recurrence. Eighty-three percent (781) of the 947 patients were white. The median clinical tumor size at diagnosis was similar among the three groups. Among the 947 patients, 461 (56%) presented with stage I disease, and 361 (44%) had stage II disease. Clinically palpable lymph nodes were found in 59 patients (6%).


View this table:
[in this window]
[in a new window]
  		TABLE 1. Demographic and treatment characteristics
 
An ALND was performed in 800 patients (85%; 86% of the patients with no recurrence, 77% of the patients with LRR, and 66% of the patients with LRR+SR). Hence, lumpectomy without ALND was performed in significantly more patients with LRR or LRR+SR than in patients with no recurrence (28% vs. 14%; P < .001). Patterns of LRR for lumpectomy versus lumpectomy plus ALND were breast alone in 80% vs. 89%, breast plus axilla in 9% vs. 6%, and axilla alone in 11% vs. 6%, respectively (P = .127). All patients were given radiotherapy, and there were no differences in the use of a radiation boost among the groups. Adjuvant systemic therapy was given to 41% (388) of the 947 patients (19% of the 125 patients with LRR or LRR+SR and 44% of the 822 patients with no recurrence; P < .001). Twenty-five percent (233) of the 947 patients were given chemotherapy; significantly more patients without recurrence were given chemotherapy than patients with LRR or LRR+SR (26% vs. 19%; P = .009). Hormonal therapy was given to 20% (193) of the 947 patients (6% of the 125 patients with LRR or LRR+SR and 23% [186] of the 822 patients without recurrence; P < .001).

Pathologic Characteristics
Tumor histological characteristics are listed in Table 2. The median pathologic tumor diameter was 1.5 cm (range, .0–7.0 cm). The median tumor size was larger in patients with LRR or LRR+SR than in patients with no recurrence (1.8 vs. 1.5 cm; P = .006). Seventy-five percent of the 947 patients presented with invasive ductal carcinoma with or without an in situ component. Patients for whom data on estrogen-receptor status or progesterone-receptor status were not available were excluded from analysis. Among the remaining patients, no differences in estrogen- or progesterone-receptor status were found among the groups. Information on nuclear grade was available for 64% of tumors; of these tumors, 36% were poorly differentiated, 55% were moderately differentiated, and 9% were well differentiated. No significant differences in nuclear grade were found with regard to recurrence.


View this table:
[in this window]
[in a new window]
  		TABLE 2. Histological characteristics
 
In contrast, pathologic margin status was significantly different among the three groups after exclusion of patients for whom margin status was unknown. Approximately 80% of patients with no recurrence had known negative margins, compared with 65% of the patients with LRR or LRR+SR (P = .037). The incidence of axillary lymph node involvement was similar among the three groups, ranging from 23% to 35%, and was highest among the LRR+S patients (P = .289).

Outcome Characteristics
Recurrence and survival are listed in Table 3. The median overall follow-up time was 9 years (range, 3 months to 29 years). The median follow-up time was longer for patients with LRR or LRR+SR than for patients with no recurrence (P < .001). It is interesting to note that the incidence of metachronous contralateral breast carcinoma was higher in the LRR group than in the other groups (17% vs. 7%; P = .006). Among the 12 patients with LRR who developed contralateral breast carcinomas, 4 (7%) later developed systemic disease and died of breast cancer.


View this table:
[in this window]
[in a new window]
  		TABLE 3. Outcomes
 
The site of LRR was no different (P = .204) between patients with LRR and those with LRR+SR. The majority (87%) of LRRs developed in the breast, although eight patients (6%) presented with breast and axillary recurrence and nine patients (7%) presented with axillary recurrence only.

Twenty-year disease-specific survival rates were 100% for patients with no recurrence and those with only LRR. These rates were significantly different (P < .001) from those for patients who later developed SR (Fig. 1). Similarly, 20-year LRR-free survival rates were significantly different among the three groups (Fig. 2). However, these rates were no different between the LRR and the LRR+SR groups (P = .309).



View larger version (18K):
[in this window]
[in a new window]
  		FIG. 1. Disease-specific survival rates for patients with locoregional recurrence alone (LRR), locoregional recurrence followed by systemic recurrence (LRR+S), or no recurrence (NR).

 


View larger version (18K):
[in this window]
[in a new window]
  		FIG. 2. Locoregional recurrence-free survival rates for patients with locoregional recurrence alone (LRR), locoregional recurrence followed by systemic recurrence (LRR+S), or no recurrence (NR).

 
Characteristics of LRR
The clinical and pathologic characteristics at local recurrence among LRR and LRR+SR patients are listed in Table 4. The median age at recurrence was 51 years (range, 30–84 years) and was similar among patients with LRR and those with LRR+SR. The median time to LRR was 5 years (range, 1.2 months to 23 years) and was similar between groups (5 vs. 4 years; P = .201). Tumor size at recurrence was significantly larger among patients with LRR+SR than among those with LRR only (P = .006). Most of these recurrences were detected by either physical examination or mammography. Most of the patients who experienced disease recurrence were treated with completion mastectomy, with or without chemotherapy and with or without hormonal therapy; however, 11 (9%) of 125 patients underwent re-excision of the recurrent tumor rather than mastectomy followed by chemotherapy with or without hormonal therapy. Among the recurrent tumors, more than half were invasive ductal or invasive lobular carcinoma with or without an in situ component, but 11% were found to be ductal carcinoma-in-situ alone. However, pathology reports were not available for review for 38 patients (30%) who were treated for recurrence at an outside facility. Information regarding estrogen- or progesterone-receptor status and Black’s nuclear grade was available for only 26% and 50%, respectively, of the patients with disease recurrence. Information on tumor ploidy, lymphovascular invasion, lymph node metastasis, and extranodal extension also was not available for a sufficient number of patients to draw any meaningful conclusions.


View this table:
[in this window]
[in a new window]
  		TABLE 4. Patient and tumor characteristics at local recurrence
 
Univariate Predictors
Significant predictors of LRR by univariate analysis are listed in Table 5. Young age (<=50 years) at initial diagnosis, large tumor size (>1.5 cm), positive margins, and treatment with lumpectomy without ALND correlated with the development of LRR. In contrast, patients who were given chemotherapy or hormonal therapy were less likely to develop LRR after BCT. Finding no difference in these characteristics between the LRR and LRR+SR groups, we then combined these two groups and compared this combined with-recurrence group with the no-recurrence group to identify any independent predictors of LRR in multivariate analysis.


View this table:
[in this window]
[in a new window]
  		TABLE 5. Univariate analysis of significant predictors of locoregional recurrence
 
Multivariate Model
Results from multivariate analysis of predictors of LRR are listed in Table 6. Young age (P < .001), large tumor size (P = .017), positive lymph nodes (P = .003), not receiving chemotherapy (P < .001), and not receiving hormonal therapy (P = .025) were significant independent predictors of LRR in our study population. Specifically, patients who were 50 years of age or younger were four times more likely to develop LRR than were those who were older than 50 years. Patients with positive axillary lymph nodes were three times more likely to develop LRR, and those with tumors larger than 1.5 cm were twice as likely to develop LRR. Patients who were given chemotherapy were 78% less likely to develop LRR, and patients who were given hormonal therapy were 66% less likely to develop LRR.


View this table:
[in this window]
[in a new window]
  		TABLE 6. Independent predictors of locoregional recurrence after breast-conservation therapy
 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
CONCLUSIONS
 REFERENCES
 
In this study, the overall LRR rate after BCT was 11% at a median follow-up of 9 years, a rate similar to those reported for either BCT or mastectomy performed in large prospective randomized trials. In those trials, local recurrence rates for patients treated with BCT ranged from 5% to 20%, and those for patients treated with mastectomy ranged from 2% to 19%. The broad range of follow-up time in these studies (6–19 years) may account for the range of recurrence rates.9,13–17 Results from a trial conducted by investigators at the National Cancer Institute15 showed that the local recurrence rates for patients with early-stage breast cancer treated with BCT were 12% and 20% at 5 and 10 years, respectively. Except for a trial conducted in Milan,13 none of the other prospective trials had a follow-up time longer than 12 years. This study provides information with an overall follow-up time of nearly 30 years (median, 9 years), which is longer than that of other published series.

The incidence of contralateral breast cancer among patients with LRR in our study was significantly higher than that among patients with no recurrence. Kurtz et al.32 also observed that the relative risk for the development of contralateral breast cancer was 1.64 for patients with recurrence in the ipsilateral breast and 1.28 for patients with a family history of breast cancer. In our study, complete information regarding family history was not available for enough patients to draw any conclusions regarding this variable.

Risk factors for local recurrence reported in the literature have included patient age; tumor histology, grade, and size; positive tumor margins; multifocality; multiple tumors; extent of intraductal component; nodal status; lymphatic or vascular invasion; major stromal reaction; and increased levels of p53. Although we could not assess all of these factors, we found that young age, large tumor size, positive lymph nodes, and the lack of chemotherapy or hormonal therapy were independent predictors of LRR in early-stage invasive breast cancer.

Age <40 or even <35 years has been found to be a risk factor for the development of local recurrence after BCT in some studies,7,11,19–22,24,33–37 but not in others.38,39 This has also been described in young patients undergoing mastectomy for treatment of their primary tumor.16 Other studies have found no difference in local recurrence rates when patients younger than 50 years were compared with those older than 50 years.40 Stotter et al.22 and Mate et al.38 found that the risk for LRR was significantly increased among patients <50 years of age. In our study, we found that the most significant cutoff for age was 50 years (corresponding approximately to the age of menopause). Only 11% of patients presented at age <35 years, and only 22% presented at age <40 years. These findings suggest that breast cancer in young women may have a different biological behavior, 41 and optimal treatment planning should be considered for these patients, because they are at an increased risk for subsequent development of local recurrence.42

Larger tumor size has also been found to be a risk factor for local recurrence among patients with early-stage breast cancer treated with BCT. In some studies, patients with tumors larger than 2 cm on histological examination were at increased risk of developing local recurrence, particularly those who were not given radiotherapy.16,33,43 Fisher et al.44 found that tumor size of more than 5 cm was the only risk factor for LRR in multivariate analysis of patients with stage II or III axillary node-positive breast cancer; these patients were given adjuvant chemotherapy but not locoregional radiation after segmental or modified radical mastectomy. We found tumor size to be an independent risk factor for the development of LRR; we used 1.5 cm as a cutoff because that was the median tumor size in our population.

Prognostic factors for local recurrence are controversial.33 Surveillance, Epidemiology, and End Results data on 24,740 patients with breast cancer from 1977 to 1982 showed a linear relationship between tumor size and node status; larger tumors and positive nodes were independent prognostic indicators and negatively influenced survival.45 Swenson et al.46 concluded that positive lymph nodes and estrogen receptor-negative status were the only factors predictive of disease recurrence after BCT. These investigators were unable to find any prognostic factor for local recurrence in their study. In contrast, we found that patients with positive axillary lymph nodes were three times more likely to develop LRR and that almost half of those who developed recurrent disease subsequently developed distant metastases, with correspondingly poor outcome.

Several studies have reported a reduction in local recurrence rates for patients treated with BCT followed by adjuvant chemotherapy.10,47,48 The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-06 trial compared mastectomy, lumpectomy, and lumpectomy with radiotherapy for stage I and II breast cancer and included adjuvant chemotherapy for node-positive patients. Chemotherapy led to a marked reduction in local recurrence rate.10 Another NSABP trial of adjuvant chemotherapy versus placebo for patients with node-negative disease showed similar results for patients treated with mastectomy or BCT.47 We found that the risk of LRR can be reduced by approximately 80% when early-stage breast cancer is treated with adjuvant chemotherapy.

The NSABP B-14 trial of tamoxifen versus placebo among estrogen receptor-positive and node-negative patients showed that tamoxifen reduced not only local recurrence, but also the development of contralateral breast cancer.48 The NSABP B-24 trial demonstrated a 42% reduction in the development of contralateral breast cancer in patients with intraductal breast tumors treated with tamoxifen. These patients were also found to have a decreased rate of local recurrence.49 Patients in our study who were given adjuvant hormonal therapy were 66% less likely to develop LRR than those who were not given hormonal therapy.

Positive tumor margins have also been shown to influence the development of local recurrence after BCT.24,33,35,50–52 Because <10% of the patients in our study had a positive tumor margin, we could not evaluate possible correlation of margin status with LRR in the final multivariate model. Other reported risk factors for the development of local recurrence have been described, including a high extent of intraductal component,19–21,24,26,27,35,36,41,53,54 high tumor grade, 19,20,24,28 multifocality,24,34 multiple tumors,7,19,22,24,25,33 lymphatic or vascular invasion,19,24,33,35,36,43 major stromal reaction,19,24 and increased levels34 of p53. Because our study was retrospective in nature, data on these factors were not available for sufficient numbers of patients to draw meaningful conclusions.

Kemperman et al.55 found local recurrence to be a risk factor for poor disease-specific survival but did not describe the exact mechanism by which the local recurrence influences survival. Some studies have reported that the development of local recurrence after BCT is a marker for poor prognosis, as it is for patients who develop local recurrence after mastectomy.56,57 This was found to be true in the European Organization for Research and Treatment of Cancer trial comparing radical mastectomy and BCT.16

In our population, disease-specific survival among patients with LRR alone was superior to that among patients with LRR followed by SR; almost half of the LRRs were associated with subsequent development of distant metastases, and among these only 18% were alive with disease at the last follow-up.


   CONCLUSIONS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
REFERENCES
 
In conclusion, independent predictors of an increased risk of LRR after BCT are young age, positive lymph nodes, and large primary tumor. Patients at increased risk may be considered for adjuvant therapy, because the use of chemotherapy and hormonal therapy were statistically independent predictors of a reduced risk for LRR. Patients at increased risk of LRR after BCT also have a higher incidence of contralateral breast cancer and should be counseled about chemopreventive risk-reduction strategies. Because almost half of the LRRs in our series were associated with subsequent distant metastases, we advocate aggressive local and systemic therapy regimens for these patients.


   Acknowledgments
 
K.K.H. was supported by a Department of Defense Career Development Award (DAMD 17-97-1-7162).


   Footnotes
 
Presented at the 54th Annual Cancer Symposium of the Society of Surgical Oncology, Washington, DC, March 15–18, 2001.

Received for publication April 19, 2001. Accepted for publication November 14, 2001.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSIONS
 REFERENCES
 

  1. Haffty BG, Fischer D, Beinfield M, McKhann C. Prognosis following local recurrence in the conservatively treated breast cancer patient. Int J Radiat Oncol Biol Phys 1991; 21: 293–8.[Medline]
  2. Treatment of early-stage of breast cancer. National Institute of Health Consensus Conference. JAMA 1991; 265: 391–5.[CrossRef][Medline]
  3. Greenlee RT, Hill-Harmon MB, Murray T, Thun M. Cancer statistics, 2001. CA Cancer J Clin 2001; 51: 15–36.[Abstract/Free Full Text]
  4. Harris JR, Hellman S. The Results of Primary Radiation Therapy for Early Breast Cancer at the Joint Center for Radiation Therapy. Philadelphia: JB Lippincott, 1983.
  5. Montague ED. Conservation surgery and radiation therapy in the treatment of operable breast cancer. Cancer 1984; 53: 700–4.[CrossRef][Medline]
  6. Danoff BF, Pajak TF, Solin LJ, Goodman RL. Excisional biopsy, axillary node dissection and definitive radiotherapy for stages I and II breast cancer. Int J Radiat Oncol Biol Phys 1985; 11: 479–83.[Medline]
  7. Calle R, Vilcoq JR, Zafrani B, Vielh P, Fourquet A. Local control and survival of breast cancer treated by limited surgery followed by irradiation. Int J Radiat Oncol Biol Phys 1986; 12: 873–8.[Medline]
  8. Veronesi U, Banfi A, Salvador B, et al. Breast conservation is the treatment of choice in small breast cancer: long-term results of a randomized trial. Eur J Cancer 1990; 26: 668–70.
  9. Sarrazin D, Le MG, Arriagada R, et al. Ten-year results of a randomized trial comparing a conservative treatment to mastectomy in early breast cancer. Radiother Oncol 1989; 14: 177–84.[CrossRef][Medline]
  10. Fisher B, Redmond C, Poisson R, et al. Eight-year results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med 1989; 320: 822–8.[Abstract]
  11. Delouche G, Bachelot F, Premont M, Kurtz JM. Conservation treatment of early breast cancer: long term results and complications. Int J Radiat Oncol Biol Phys 1987; 13: 29–34.[Medline]
  12. Rayte Z, Gazet JC, Ford HT, Easton DF, Coombes RC. Comparison of conservative surgery and radiotherapy with mastectomy in the treatment of early breast cancer. Eur J Surg Oncol 1990; 16: 486–92.[Medline]
  13. Veronesi U, Luini A, Galimberti V, Zurrida S. Conservation approaches for the management of stage I/II carcinoma of the breast: Milan Cancer Institute trials. World J Surg 1994; 18: 70–5.[CrossRef][Medline]
  14. Fisher B, Redmond C. Lumpectomy for breast cancer: an update of the NSABP experience. J Natl Cancer Inst Monogr 1992; 11: 7–13.
  15. Straus K, Lichter A, Lippman M, et al. Results of the National Cancer Institute early breast cancer trial. J Natl Cancer Inst Monogr 1992; 11: 27–32.
  16. van Dongen JA, Bartelink H, Fentiman IS, et al. Randomized clinical trial to assess the value of breast-conserving therapy in stage I and II breast cancer, EORTC 10801 trial. J Natl Cancer Inst Monogr 1992; 11: 15–8.
  17. Blichert-Toft M, Rose C, Andersen JA, et al. Danish randomized trial comparing breast conservation therapy with mastectomy: six years of life-table analysis. J Natl Cancer Inst Monogr 1992; 11: 19–25.
  18. Macmillan RD, Purushotham AD, George WD. Local recurrence after breast-conserving surgery for breast cancer. Br J Surg 1995; 83: 149–55.
  19. Recht A, Connolly JL, Schnitt SJ, et al. The effect of young age on tumor recurrence in the treated breast after conservative surgery and radiotherapy. Int J Radiat Oncol Biol Phys 1987; 14: 3–10.
  20. Kurtz JM, Jacquemir J, Amalric R, et al. Risk factors for breast recurrence in premenopausal and postmenopausal patients with ductal cancers treated by conservation therapy. Cancer 1990; 65: 1867–78.[CrossRef][Medline]
  21. Boyages J, Recht A, Connolly JL, et al. Early breast cancer: predictors of breast recurrence for patients treated with conservative surgery and radiation therapy. Radiother Oncol 1990; 19: 29–41.[CrossRef][Medline]
  22. Stotter AT, McNeese MD, Ames FC, et al. Predicting the rate and extent of locoregional failure after breast conservation therapy for early breast cancer. Cancer 1989; 64: 2217–25.[CrossRef][Medline]
  23. Katz A, Strom EA, Buchholz T, et al. Locoregional recurrence patterns after mastectomy and doxorubicin-based chemotherapy: implications for postoperative irradiation. J Clin Oncol 2000; 18: 2817–27.[Abstract/Free Full Text]
  24. Kurtz JM, Jacquemir J, Amalric R, et al. Why are local recurrences after breast-conserving therapy more frequent in younger patients? J Clin Oncol 1990; 8: 591–8.[Abstract]
  25. Miller A, von Fournier D, Kaufmann M, et al. Whole breast irradiation and boost irradiation in breast conserving therapy based on morphologic findings. Breast Dis 1989; 2: 121–30.
  26. Eberlein TJ, Connolly JL, Schnitt SJ, et al. Predictors of local recurrence following conservative breast surgery and radiation therapy: the influence of tumor size. Arch Surg 1990; 125: 771–7.[Abstract]
  27. Jacquemier J, Kurtz JM, Amalric R, et al. An assessment of extensive intraductal component as a risk factor for local recurrence after breast-conserving therapy. Br J Cancer 1990; 61: 873–6.[Medline]
  28. Clark RM, McCulloch PB, Levine MN, et al. Randomized clinical trial to assess the effectiveness of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer. J Natl Cancer Inst 1992; 84: 683–9.[Abstract/Free Full Text]
  29. Hunt K, Singletary SE, Smith TL, et al. Conservation surgery and radiation: the M.D. Anderson Cancer Center experience.In: Bland KI, Copeland EM, eds. The Breast: Comprehensive Management of Benign and Malignant Disease. Philadelphia: WB Saunders, 1998: 1179–82.
  30. Buzdar AU, Hortobagyi GN, Kau SW. Breast Cancer Adjuvant Therapy at the M. D. Anderson Cancer Center: Results of Four Prospective Studies. Philadelphia: JB Lippincott, 1993.
  31. Kaplan El, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–81.[CrossRef]
  32. Kurtz JM, Amalric R, Brandone H, Ayme Y, Spitalier JM. Contralateral breast cancer and other second malignancies in patients treated by breast-conserving therapy with radiation. Int J Radiat Oncol Biol Phys 1988; 15: 277–84.[CrossRef][Medline]
  33. Borger JH. The impact of surgical and pathological findings on radiotherapy of early breast cancer. Radiother Oncol 1991; 22: 230–6.[CrossRef][Medline]
  34. Elkhuizen PHM, van Slooten H-J, Clahsen PC, et al. High local recurrence risk after breast-conserving therapy in node-negative premenopausal breast cancer patients is greatly reduced by one course of perioperative chemotherapy: a European Organization for Research and Treatment of Cancer Breast Cancer Cooperative Group study. J Clin Oncol 2000; 18: 1075–83.[Abstract/Free Full Text]
  35. Borger J, Kemperman H, Hart A, et al. Risk factors in breast conservation therapy. J Clin Oncol 1994; 12: 653–60.[Abstract]
  36. Voogd AC, Nielsen M, Peterse JL, et al. Differences in risk factors for local and distant recurrence after breast-conserving therapy or mastectomy for stage I and II breast cancer: pooled results of two large European randomized trials. J Clin Oncol 2001; 19: 1688–97.[Abstract/Free Full Text]
  37. Kurtz JM, Spitalier JM, Amalric R, et al. Mammary recurrences in women younger than forty. Int J Radiat Oncol Biol Phys 1988; 15: 271–6.[CrossRef][Medline]
  38. Mate TP, Carter D, Fisher DB, et al. A clinical and histopathologic analysis of the results of conservation surgery and radiation therapy in stage I and II breast carcinoma. Cancer 1986; 58: 1995–2002.[CrossRef][Medline]
  39. Solin LJ, Fowble B, Schultz DJ, et al. Age as a prognostic factor for patients with definitive irradiation for early stage breast cancer. Int J Radiat Oncol Biol Phys 1989; 16: 373–81.[Medline]
  40. Nobler MP, Venet L. Prognostic factors in patients undergoing curative irradiation for breast cancer. Int J Radiat Oncol Biol Phys 1985; 11: 1323–31.[Medline]
  41. Bartelink H, Borger J, van Dongen J, et al. The impact of tumor size and histology on local control after breast conserving therapy. Radiother Oncol 1988; 11: 297–303.[CrossRef][Medline]
  42. Elkhuizen PHM, van de Vijver MJ, Hermans J, et al. Local recurrence after breast conserving treatment: high incidence in young patients and association with poor survival. Int J Radiat Oncol Biol Phys 1998; 40: 859–67.[CrossRef][Medline]
  43. Fisher B, Anderson S. Conservative surgery for the management of invasive and noninvasive carcinoma of the breast: NSABP trials. National Surgical Adjuvant Breast and Bowel Project. World J Surg 1994; 18: 63–9.[CrossRef][Medline]
  44. Fisher BJ, Perera FE, Cooke AL, et al. Long-term follow-up of axillary node-positive breast cancer patients receiving adjuvant systemic therapy alone: patterns of recurrence. Int J Radiat Oncol Biol Phys 1997; 38: 541–50.[CrossRef][Medline]
  45. Carter CL, Allen C, Henson DE. Relation of tumor size, lymph node status and survival in 24,740 breast cancer cases. Cancer 1988; 63: 181–7.
  46. Swenson KK, Decher L, Haselow R, et al. Prognostic factors after conservative surgery and radiation therapy for early stage breast cancer. Am J Clin Oncol 1998; 21: 111–6.[CrossRef][Medline]
  47. Fisher B, Redmond C, Dimitrov NV, et al. A randomized clinical trial evaluating sequential methotrexate and fluorouracil in the treatment of patients with node-negative breast cancer who have estrogen-receptor-negative tumors. N Engl J Med 1989; 320: 473–8.[Abstract]
  48. Fisher B, Constantino J, Redmond C, et al. A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors. N Engl J Med 1989; 320: 479–84.[Abstract]
  49. Fisher B, Dignam J, Wolmark N, et al. Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B-24 randomized controlled trial. Lancet 1999; 353: 1993–2000.[CrossRef][Medline]
  50. Di Biase S, Komarnicky LT, Schwartz GF, et al. The number of positive margins influences the outcome of women treated with breast preservation for early stage breast carcinoma. Cancer 1998; 82: 2212–20.[CrossRef][Medline]
  51. Smitt MC, Nowels KW, Zdeblick MJ, et al. The importance of the lumpectomy surgical margin status in long term results of breast conservation. Cancer 1995; 76: 259–67.[CrossRef][Medline]
  52. Schmitt SJ, Abner A, Gelman R, et al. The relationship between microscopic margins of resection and the risk of local recurrence in patients with breast cancer treated with breast-conserving surgery and radiation therapy. Cancer 1994; 74: 1746–51.[CrossRef][Medline]
  53. Voogd AC, Peterse JL, Crommelin MA, et al. Histological determinants for different types of local recurrence after breast-conserving therapy of invasive breast cancer. Eur J Cancer 1999; 35: 1828–37.
  54. Veronesi U, Marubini E, Del Vecchio M, et al. Local recurrences and distant metastases after breast-conserving treatments: partly independent events. J Natl Cancer Inst 1995; 87: 19–27.[Abstract/Free Full Text]
  55. Kemperman H, Borger J, Hart A, et al. Prognostic factors for survival after breast conserving therapy for stage I and II breast cancer. The role of local recurrence. Eur J Cancer 1995; 31A: 690–8.
  56. Chauvet B, Reynaud-Bougnoux A, Calais G, et al. Prognostic significance of breast relapse after conservative treatment in node-negative early breast cancer. Int J Radiat Oncol Biol Phys 1990; 19: 1125–30.[Medline]
  57. Whelan T, Clark R, Roberts R, et al. Ipsilateral breast tumor recurrence post lumpectomy is predictive of subsequent mortality: results from a randomized trial. Int J Radiat Oncol Biol Phys 1994; 30: 11–6.[Medline]



This article has been cited by other articles:


Home page
 Ann. Surg. Oncol.Home page
T. P. Olson, J. Harter, A. Munoz, D. M. Mahvi, and TM. Breslin
Frozen Section Analysis for Intraoperative Margin Assessment During Breast-Conserving Surgery Results in Low Rates of Re-excision and Local Recurrence
Ann. Surg. Oncol., October 1, 2007; 14(10): 2953 - 2960.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
L. A. Newman and H. M. Kuerer
Advances in Breast Conservation Therapy
J. Clin. Oncol., March 10, 2005; 23(8): 1685 - 1697.
[Full Text] [PDF]

Home page
 JCOHome page
A. M. Chen, F. Meric-Bernstam, K. K. Hunt, H. D. Thames, M. J. Oswald, E. D. Outlaw, E. A. Strom, M. D. McNeese, H. M. Kuerer, M. I. Ross, et al.
Breast Conservation After Neoadjuvant Chemotherapy: The M.D. Anderson Cancer Center Experience
J. Clin. Oncol., June 15, 2004; 22(12): 2303 - 2312.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Surg. Oncol.Home page
S.T. Hollenbeck, C. Cellini, P. Christos, Y. Varnado-Rhodes, D. Martins, M. Nussbaum, M.P. Osborne, and R.M. Simmons
Breast Cancer in Patients With Residual Invasive Carcinoma is More Accurately Staged With Additive Tumor Size Assessment
Ann. Surg. Oncol., January 1, 2004; 11(1): 59 - 64.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Surg. Oncol.Home page
F. Darvishian, S. I. Hajdu, and D. C. DeRisi
Significance of Linear Extent of Breast Carcinoma at Surgical Margin
Ann. Surg. Oncol., January 1, 2003; 10(1): 48 - 51.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mirza, N. Q.
Right arrow Articles by Hunt, K. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mirza, N. Q.
Right arrow Articles by Hunt, K. K.
Related Collections
Right arrow Sentinel lymph node

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS