This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rouzier, R. Articles by Bourstyn, E. Search for Related Content PubMed PubMed Citation Articles by Rouzier, R. Articles by Bourstyn, E. Social Bookmarking                            What's this?

Primary Chemotherapy for Operable Breast Cancer: Incidence and Prognostic Significance of Ipsilateral Breast Tumor Recurrence After Breast-Conserving Surgery

From the Departments of Surgery, Biostatistics, Oncology, Radiotherapy, and Pathology, Institut Curie, Paris, France.

Address reprint requests to Edwige Bourstyn, MD, Department of Surgery, 26 rue d’Ulm, 75005 Paris, France; email: edwige.bourstyn{at}curie.net

	ABSTRACT

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION REFERENCES

 
PURPOSE: To determine the incidence and the prognostic value of ipsilateral breast tumor recurrence (IBTR) in patients treated with primary chemotherapy and breast-conserving surgery.

PATIENTS AND METHODS: Between January 1985 and December 1994, 257 patients with invasive T1 to T3 breast carcinoma were treated with primary chemotherapy, lumpectomy, and radiation therapy. The median follow-up time was 93 months. To evaluate the role of IBTR in metastase-free survival, a Cox regression multivariate analysis was performed using IBTR as a time-dependent covariate.

RESULTS: The IBTR rates were 16% (± 2.4%) at 5 years and 21.5% (± 3.2%) at 10 years. Multivariate analysis showed that the probability of local control was decreased by the following independent factors: age 40 years, excision margin 2 mm, S-phase fraction more than 4%, and clinical tumor size more than 2 cm at the time of surgery. In patients with excision margins of more than 2 mm, the IBTR rates were 12.7% at 5 years and 17% at 10 years. Nodal status, age 40 years, and negative estrogen receptor status were predictors of distant disease in the Cox multivariate model with fixed covariates. The contribution of IBTR was highly significant (relative risk = 5.34) when added to the model, whereas age 40 years was no longer significant. After IBTR, 31.4% (± 7.0%) of patients developed metastases at 2 years and 59.7% (± 8.1%) at 5 years. Skin involvement, size at initial surgery, and estrogen receptor status were predictors of metastases after IBTR.

CONCLUSION: IBTR is a strong predictor for distant metastases. There are implications for conservative surgery after downstaging of the tumor and therapy at the time of IBTR.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION REFERENCES

 
PRIMARY CHEMOTHERAPY followed by conservative therapy is an established alternative to mastectomy in the management of large breast tumors.^1-4 Encouraging results obtained in clinically advanced breast carcinoma led clinicians to apply primary chemotherapy to smaller tumors.^3,5 With long follow-up times, randomized studies comparing primary versus adjuvant chemotherapy did not show any differences in terms of disease-free and overall survival rates but showed that primary chemotherapy led to more frequent breast-conserving surgery.^2,6-10 Two of these studies^2,7 reported that local relapses were, because of breast-conserving treatment, more frequent in the neoadjuvant group than in the adjuvant group. The pejorative significance of ipsilateral breast tumor recurrence (IBTR) has been demonstrated in early breast carcinoma,^11-14 but prognostic significance of local relapse has never been clearly evaluated in breast carcinoma treated by primary chemotherapy and conservative surgery. To identify possible predictive factors for local recurrence and increased risk for distant metastases after primary chemotherapy and conservative surgery, we conducted this retrospective study on 257 T1 to T3 breast carcinoma patients treated by primary chemotherapy and surgery in one center over a 10-year period.

	PATIENTS AND METHODS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION REFERENCES

 
Our breast cancer database was initiated in 1981 to prospectively register diagnostic, prognostic, therapeutic, pathologic, relapse, and survival data for all patients treated for breast cancer at Institut Curie. The database was used to select women referred between January 1, 1985, and December 31, 1994, who were treated by primary chemotherapy followed by surgery. The aim of this therapeutic strategy was to reduce tumor size and increase the feasibility of breast-conserving surgery for most of the patients or to control locoregionally advanced disease before surgery (metastatic involvement of axillary nodes documented by fine-needle aspiration). Patients with tumor size 3 cm after primary chemotherapy were eligible for breast-conserving surgery. Inflammatory, bilateral, T4, and metastatic tumors were excluded from the study. During this period, 460 patients met the criteria of selection: 257 had undergone breast-conserving surgery after chemotherapy, and 203 underwent a mastectomy. For the study, we restricted analysis to the 257 patients treated with breast-conserving surgery. The mean age was 47 years (range, 24 to 74 years). Fifteen patients (5.8%) had T1 tumors, 216 (84.1%) had T2 tumors, and 26 (10.1%) had T3 tumors according to the International Union Against Cancer classification. One hundred fifty-nine patients (61.9%) were clinically N0, 91 (35.4%) were N1, and seven were (2.7%) N2. All T1 patients had cytologically proven metastatic nodes.

Pathologic diagnosis and grading were performed on a tumor tissue sample obtained by core needle biopsy performed before treatment. Carcinomas corresponded to infiltrating ductal in 92% (n = 236), infiltrating lobular in 4% (n = 11), and other types in 4% (medullary, tubular, and colloid carcinoma; n = 10). Histologic grade was performed according to Scarff, Bloom, and Richarson (SBR) method and was I for 33 patients, II for 126, III for 70, and indeterminate for 28. Estrogen receptor (ER) status and S-phase fraction were determined on tumorous cells obtained by fine-needle aspiration cytology before any treatment for 228 (positive, 131; negative, 97) and 169 (83 4%; 86 > 4%) patients, respectively. The details of DNA flow cytometry have been described elsewhere.¹⁵ The samples were suspended in phosphate-buffered saline containing 0.1% of NP40 (Sigma Chemical Co, St Louis, MO), 50 µg of propidium iodide/mL (Sigma), and 0.5 mg of ribonuclease A/mL (Boehringer Mannheim Biochemicals, Indianapolis, IN) and analyzed on a FACS Analyzer I (Becton Dickinson, Mountain View, CA). The median S-phase fraction was slightly above 4%. This threshold was chosen as the cutoff value above which the proliferative index was considered to be high.

Treatment in consenting patients consisted of neoadjuvant chemotherapy, including four courses of an intravenous drug combination with anthracycline (n = 138) or without (n = 119). Because of severe toxicity or tumor progression under chemotherapy, 14 and 12 patients received, respectively, three and two courses. Table 1 details the drug combination used during this period. One hundred five patients had been included in randomized trials. Chemotherapy was administered at 28-day intervals or longer, depending on the recovery of bone marrow. Clinical response to chemotherapy was assessed by an oncologist and a surgeon. Patients in whom the initial breast tumor could not be identified on palpation were defined as complete response (n = 11). Partial response was defined as a 50% decrease of tumor size (n = 208). Minor response was defined as a decrease in the tumor insufficient to qualify for partial response (n = 25); patients experiencing stable or progressive disease were grouped for statistical analysis (n = 13). Excised tissue volume was related to postchemotherapy tumor dimensions to achieve specimen margins grossly free of tumor. Two hundred fifty-five patients had axillary dissection, and two patients received 45 Gy to the axillary nodes.

Resection margins were assessed after inking and were classified as positive in 10.9% of patients, close ( 2 mm) in 17.5%, negative ( > 2 mm) in 67.3%, and indeterminate in 4.3%. Margins that could not be determined either because the originally report did not comment on margins or because the original specimen had not been inked were called indeterminate. Margins were considered to be involved when invasive or intraductal carcinoma was present focally at the surface of the specimen (invasive or intraductal carcinoma involving the margin in three or fewer low-power microscopic fields). These patients were eligible for a radiation boost of the tumor bed. Patients with extensively involved margins underwent a mastectomy and were not included in the analysis (n = 12). All the patients but one were given postoperative radiotherapy to the breast at a mean dose of 53 Gy (range, 44 to 64 Gy). Whole-breast irradiation was followed by a supplemental boost to the tumor bed in 136 patients (52.9%). The tumor bed was boosted with external radiotherapy in 107 cases and with interstitial implantation in 29 cases (mean dose, 14 Gy; range, 5 to 25 Gy). The radiation therapy technique evolved over the study time period. The whole-breast dose was higher in the early years of the study, and the use of radiation boost in the tumor area was more frequent in the later years. Radiation boost was nevertheless given to patients with large tumors and/or focally involved margins and/or extensive intraductal components. Twenty-seven of the 28 patients with positive margins and 32 of the 44 with close margins received a boost in the tumor bed. Radiotherapy to the supraclavicular fossa was also required if there was axillary lymph node involvement at surgery or clinical evidence of axillary disease before chemotherapy (n = 123; mean dose, 44 Gy; range, 34 to 61 Gy). When the tumor was located in the inner quadrants or in the central region of the breast, the internal mammary lymph nodes were irradiated (n = 201; mean dose, 44 Gy; range, 30 to 48 Gy).

Twenty-five patients received one to five adjuvant courses of chemotherapy: 14 because they had received three preoperative courses of chemotherapy and 11 because of massive axillary involvement. Hormonal therapy (tamoxifen 20 mg/d) was prescribed for 33 postmenopausal patients with ER-positive tumors. In Institut Curie, premenopausal patients and ER-negative tumor patients were not eligible for a treatment by tamoxifen during this period.

After treatment, patients were seen alternatively by an oncologist, a radiotherapist, and a surgeon. They usually were seen every 3 months during the first 2 years, every 6 months during the next 3 years, and yearly thereafter. Median follow-up time from the date of initial histologic diagnosis for all patients alive at the time of analysis was 93 months (range, 14 to 178 months). Ninety-two percent of patients have been followed up for at least 5 years.

Frequency distributions were tested using the ² test. The primary end point was IBTR, measured from the date of first treatment to the time of last follow-up visit or IBTR. Only patients with histologically or cytologically confirmed recurrences in the ipsilateral breast were scored as having IBTR. The secondary end point was distant metastasis, measured in the same way as the primary end point. Patients with radiographic and/or clinical evidence of metastatic disease were scored as having distant metastasis. Kaplan-Meier estimates were used to calculate the IBTR-free and metastases-free survival rates. The statistical significance of the difference between survival distributions was determined by means of the log-rank test. Clinical and pathologic factors tested by univariate and multivariate analysis included patient age, initial clinical tumor size, SBR grade, ER status, S-phase fraction, clinical regression, clinical tumor size at surgery, pathologic tumor size, pathologic residual disease, margin status, initial clinical lymph node status, pathologic nodal status, chemotherapy regimen, and radiation boost. The influence of tumor characteristics on outcome was assessed in multivariate analysis by using the Cox proportional hazards model in a forward stepwise procedure. Variables with k subgroups were coded with k-1 dummy variables, yielding a nonlinear relation between two subsequent subgroups when k was more than 2. For the metastasis-free survival rate, two separate models were constructed: one without IBTR and a second including IBTR as a time-dependent covariate. All significance tests were two-tailed, and differences were considered to be statistically significant at P .05. The Cox proportional hazards model was used to compute relative risks (RRs) and 95% confidence intervals to examine the effects of prognostic variables. All analyses were done with the Biomedical Package (BMDP; Statistical Solutions, Cork, Ireland).

	RESULTS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION REFERENCES

 
At the time of analysis, 46 patients developed local recurrences. Among these patients, four had synchronous metastases and three had previous metastases. Eighty-eight patients developed distant metastases. Of these patients, 65 had isolated metastases, four had synchronous local recurrences, and 19 had previous local recurrences. Sixteen patients developed contralateral breast carcinomas. These were the first events in nine patients. The 5-year and 10-year overall survival rates of the whole population were, respectively, 79.3% and 65.2% (Fig 1).

View larger version (9K): [in this window] [in a new window]   Fig 1. Overall survival.

View larger version (9K): [in this window] [in a new window]   Fig 2. Ipsilateral breast tumor recurrence-free survival.

View larger version (10K): [in this window] [in a new window]   Fig 3. Distant disease-free survival.

	DISCUSSION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION REFERENCES

Present results were achieved on a series of 257 women for whom initial clinical and follow-up data were prospectively registered in a database. This large series of patients treated in a single institution and followed up for a median of 93 months allows us to draw some conclusions on the risk of local recurrence, distant disease, and the timing between these events. There are obvious limitations in the interpretation of the retrospective study design that must be acknowledged, however. Even if no statistical difference could be observed between the chemotherapy regimens used, heterogeneity of primary chemotherapy regimens is the main limitation of this study. Our results have to be confirmed by studies in which patients receive a uniform chemotherapy protocol. Moreover, whether more aggressive primary chemotherapy, such as integration of doxorubicin and taxanes, will be more efficient in local control has to be assessed by further studies.

The IBTR rates in our series were 16% at 5 years and 21.5% at 10 years after neoadjuvant chemotherapy and breast-conserving surgery (Fig 2). In comparison, the 5-year and 10-year local relapse rates were 5.8% and 11.6%, respectively, for the 203 patients registered in our database during the same period and treated by primary chemotherapy and mastectomy (data not shown). The IBTR rates after breast-preserving surgery in our series are similar to those reported by Mauriac et al² comparing preoperative versus postoperative chemotherapy in breast carcinoma larger than 3 cm (22.6% at 10 years) and by the National Surgical Adjuvant Breast and Bowel Project B-18 trial⁷ (approximately 15% at 5 years in downstaged patients considered as candidates for mastectomy before entering the trial). In contrast, IBTR rate was 6.8% at 5 years in the retrospective study of the Milan Cancer Institute although only women with tumors that measured 2.5 cm had been included.⁴ Patients have to be informed of the high risk of IBTR and subsequent mastectomy to avoid serious concern in case of local recurrence.

In accordance with series studying local recurrence after lumpectomy for early breast cancer, we demonstrated that the majority of IBTR developed near the site of the primary tumor. Positive or 2 mm margins were significantly associated with IBTR in the univariate analysis (Table 2). Local control was better in positive margin group than in 2 mm margin group, possibly because a higher proportion of radiation boost was performed in the positive margin group (P = .01) than in the 2 mm group. These results underscore the potential need for a systematic radiation boost after breast-conserving surgery after primary chemotherapy even if excision margins are clear but close ( 2 mm). In Fisher et al,⁷ the high IBTR rate in patients with large tumors who have been downstaged by primary chemotherapy should not negate the use of lumpectomy because of the absence of systematic use of radiation boost and postoperative tamoxifen in their study. In our study, radiation boost was not associated with an improvement of local control, but the selection of patients eligible for this treatment may have introduced a bias. So the favorable effects of radiation boost after primary chemotherapy and conservative surgery cannot be established by our study and have to be appraised by randomized studies. In the group of patients with minor response ( 50%) or with absence of response, positive or 2 mm margins rate was 43% and local control failure was 20% at 5 years, which demonstrates the difficulty of fulfilling criteria of radicality and satisfactory cosmetic outcome. The local recurrence rates were 12.7% at 5 years and 17% at 10 years in the group of patients in whom excision margins of more than 2 mm could be achieved (Table 2). This rate is higher than the one reported by the Milan Cancer Institute.⁴ Their low rate of IBTR can be explained by the surgical technique adopted by this team: quadrantectomy by a skin incision guided by tattoo marks and not lumpectomy. This team has demonstrated the superiority of quadrantectomy over lumpectomy in early breast cancer in terms of local control but not in terms of distant disease-free survival.¹⁷ For early breast cancer, patients with tumors 3 cm are eligible for breast-conserving surgery. This size has also been considered by our team as the limit for breast-sparing surgery after neoadjuvant chemotherapy. We demonstrated that clinical size of tumors more than 2 cm at surgery was associated with a higher risk of IBTR in the multivariate model (Table 3). But breast volume was not taken into consideration in our study, and further studies are necessary to evaluate if the threshold of residual size after primary chemotherapy that permits safe conservative surgery has to be decreased from 3 to 2 cm.

Several studies have documented higher local and distant relapses in young breast cancer patients either in early breast carcinoma or breast carcinoma treated by neoadjuvant chemotherapy.^7,18-20 Whereas age 40 years was an independent predictor of survival without distant metastases in the multivariate analysis with fixed covariates, this variable did not reach statistical significance when IBTR was entered as a time-dependent covariate in the multivariate model (Tables 4 and 5). There seemed to be a correlation between the poorest prognosis of patients aged 40 years and their high rate of IBTR. Absence of systematic prescription of tamoxifen in premenopausal patients may be one of the explanations of the generally pejorative prognosis of young patients.⁷ Breast tumors of young patients display biologic markers of aggressiveness and proliferation (SBR III, ER negativity, mutated tumor suppressor gene p53, and high S-phase fraction), which is the main explanation of better response to chemotherapy but also a correlation with shorter disease-free survival times.^21-23 Our findings indicate that the age of patients has to be taken into account for the decision of breast-conserving surgery after primary chemotherapy. Additional studies are needed to clarify the factors responsible for the increased risk of IBTR in young patients.

This study clearly demonstrates for the first time that, as it has been reported for local relapse after lumpectomy for early breast cancer,^11-14,24 IBTR is a powerful independent predictor of distant disease (Table 5). The rates of distant disease-free survival after IBTR were lower in our series (68.6% at 2 years and 40.3% at 5 years) than in series studying IBTR after lumpectomy for early breast cancer in which disease-free rates of 47% to 78% at 5 years have been reported after IBTR.^13,24-28 In our series, we compared early ( 36 months) and late (> 36 months) IBTR. The cutoff at 36 months was chosen because it is the median time to breast relapse. The RR of an early IBTR was much greater than risk of late IBTR (6.15 v 3.22). The observation that earlier recurrences tend to have a less favorable prognosis is in accordance with reports on IBTR in early breast cancer.^13,24-28 But, as late local recurrence is also an independent predictor of distant metastases, it justifies considerations of systemic therapy at the time of local relapse. In early breast cancer, risk factors of distant disease after IBTR include skin invasion, early local relapse, initial T2, and positive nodes.^14,25,29,30 Except for nodal status, high-risk factors were similar in our series (Table 6). But prognosis after IBTR is poor and stresses the difficulty of selecting low-risk patients who do not need aggressive systemic treatment.

In conclusion, our study suggests that an improvement of local control may be achieved by carefully selecting patients eligible for conservative treatment. Our results have to be confirmed by studies where systemic and radiation treatment modalities were given in a uniform fashion. Local therapy after primary chemotherapy has never been evaluated by randomized studies, and prospective studies are needed to evaluate whether breast-conserving surgery is a feasible treatment of downstaged tumors, particularly in women aged 40 years or younger or with residual tumors of more than 2 cm. Risk factors of IBTR determined from this study (age 40, clinical tumor size > 2 cm after primary chemotherapy, high S-phase fraction, and poor margin status) may help either in choosing a surgical procedure after primary chemotherapy or in selecting patients eligible for entering onto trials that compare local therapies after primary chemotherapy. Conserving therapy must be discussed cautiously in case of association with these risk factors. IBTR after primary chemotherapy, breast-conserving surgery, and radiotherapy is a powerful independent predictor of distant disease and may justify chemotherapy in association with mastectomy.

	REFERENCES

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION REFERENCES

 
1. Scholl SM, Fourquet A, Asselain B, et al: Neoadjuvant versus adjuvant chemotherapy in premenopausal patients with tumours considered too large for breast-conserving surgery: Preliminary results of a randomised trial—S6. Eur J Cancer 30A: 645-652, 1994

2. Mauriac L, MacGrogan G, Avril A, et al: Neoadjuvant chemotherapy for operable breast carcinoma larger than 3 cm: A unicentre randomized trial with a 124-month median follow-up. Ann Oncol 10: 47-52, 1999[Abstract/Free Full Text]

3. Fisher B, Brown A, Mamounas E, et al: Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: Findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol 15: 2483-2493, 1997[Abstract/Free Full Text]

4. Bonadonna G, Valagussa P, Brambilla C, et al: Primary chemotherapy in operable breast cancer: Eight-year experience at the Milan Cancer Institute. J Clin Oncol 16: 93-100, 1998[Abstract/Free Full Text]

5. Powles TJ, Hickish TF, Makris A, et al: Randomized trial of chemoendocrine therapy started before or after surgery for treatment of primary breast cancer. J Clin Oncol 13: 547-552, 1995[Abstract/Free Full Text]

6. Broet P, Scholl SM, de la Rochefordiere A, et al: Short- and long-term effects on survival in breast cancer patients treated by primary chemotherapy: An updated analysis of a randomized trial. Breast Cancer Res Treat 58: 151-156, 1999[Medline]

7. Fisher B, Bryant J, Wolmark N, et al: Effect of preoperative chemotherapy on outcome of women with operable breast cancer. J Clin Oncol 16: 2672-2685, 1998[Abstract]

8. Makris A, Powles TJ, Ashley SJ, et al: A reduction in the requirements for mastectomy in a randomized trial of neoadjuvant chemoendocrine therapy in primary breast cancer. Ann Oncol 9: 1179-1184, 1998[Abstract/Free Full Text]

9. Danforth D, Jacobson J, O’Shaughnessy J, et al: Effect of preoperative chemotherapy on axillary lymph node metastases in stage II breast cancer: A prospective randomized trial. Proc Am Soc Clin Oncol 14: 128, 1995 (abstr 213)

10. Semiglazov ZF, Topuzov EE, Bavli JL, et al: Primary (neoadjuvant) chemotherapy and radiotherapy compared with radiotherapy alone in stage IIb-IIIa breast cancer. Ann Oncol 5: 591-595, 1994[Abstract/Free Full Text]

11. 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 19: 1125-1130, 1990[Medline]

12. Fisher B, Anderson S, Fisher ER, et al: Significance of ipsilateral breast tumor recurrence after lumpectomy. Lancet 338: 327-331, 1991[Medline]

13. Touboul E, Buffat L, Belkacemi Y, et al: Local recurrences and distant metastases after breast-conserving surgery and radiation therapy for early breast cancer. Int J Radiat Oncol Biol Phys 43: 25-38, 1999[Medline]

14. Fortin A, Larochelle M, Laverdiere J, et al: Local failure is responsible for the decrease in survival for patients with breast cancer treated with conservative surgery and postoperative radiotherapy. J Clin Oncol 17: 101-109, 1999[Abstract/Free Full Text]

15. Remvikos Y, Beuzeboc P, Zajdela A, et al: Correlation of pretreatment proliferative activity of breast cancer with the response to cytotoxic chemotherapy. J Natl Cancer Inst 81: 1383-1387, 1989[Abstract/Free Full Text]

16. Vincent-Salomon A, Carton M, Freneaux P, et al: ERBB2 overexpression in breast carcinomas: No positive correlation with complete pathological response to preoperative high-dose anthracycline-based chemotherapy. Eur J Cancer 36: 586-591, 2000

17. Mariani L, Salvadori B, Marubini E, et al: Ten-year results of a randomised trial comparing two conservative treatment strategies for small-size breast cancer. Eur J Cancer 34: 1156-1162, 1998

18. De La Rochefordiere A, Asselain B, Campana F, et al: Age as prognostic factor in premenopausal breast carcinoma. Lancet 341: 1039-1043, 1993[Medline]

19. Smith IE, Jones AL, O’Brien ME, et al: Primary medical (neo-adjuvant) chemotherapy for operable breast cancer. Eur J Cancer 29A: 1796-1799, 1993

20. Touboul E, Buffat L, Lefranc JP, et al: Possibility of conservative local treatment after combined chemotherapy and preoperative irradiation for locally advanced noninflammatory breast cancer. Int J Radiat Oncol Biol Phys 34: 1019-1028, 1996[Medline]

21. Nixon AJ, Neuberg D, Hayes DF, et al: Relationship of patient age to pathologic features of the tumor and prognosis for patients with stage I or II breast cancer. J Clin Oncol 12: 888-894, 1994[Abstract/Free Full Text]

22. Braud AC, Asselain B, Scholl S, et al: Neoadjuvant chemotherapy in young breast cancer patients: Correlation between response and relapse? Eur J Cancer 35: 392-397, 1999

23. Walker RA, Lees E, Webb MB, et al: Breast carcinomas occurring in young women (< 35 years) are different. Br J Cancer 74: 1796-1800, 1996[Medline]

24. Veronesi U, Marubini E, Del Vecchio M, et al: Local recurrences and distant metastases after conservative breast cancer treatments: Partly independent events. J Natl Cancer Inst 87: 19-27, 1995[Abstract/Free Full Text]

25. Kurtz JM, Amalric R, Brandone H, et al: Local recurrence after breast-conserving surgery and radiotherapy. Cancer 63: 1912-1917, 1989[Medline]

26. Abner AL, Recht A, Eberlein T, et al: Prognosis following salvage mastectomy for recurrence in the breast after conservative surgery and radiation therapy for early-stage breast cancer. J Clin Oncol 11: 44-48, 1993[Abstract]

27. Haffty BG, Reiss M, Beinfeld M, et al: Ipsilateral breast tumor recurrence as a predictor of distant disease: Implications for systemic therapy at the time of local relapse. J Clin Oncol 14: 52-57, 1996[Abstract]

28. Voogd AC, van Tienhoven G, Peterse HL, et al: Local recurrence after breast conservation therapy for early stage breast carcinoma. Cancer 85: 437-446, 1999[Medline]

29. Fourquet A, Campana F, Zafrani B, et al: Prognostic factors of breast recurrence in the conservative management of early breast cancer: A 25-year follow-up. Int J Radiat Oncol Biol Phys 17: 719-725, 1989[Medline]

30. Haffty BG, Fischer D, Beinfeld M, et al: Prognosis following local recurrence in the conservatively treated breast cancer patient. Int J Radiat Oncol Biol Phys 21: 293-298, 1991[Medline]

Submitted January 9, 2001; accepted May 31, 2001.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				K. Kiel Changing Concepts in Radiation Therapy for Early Breast Cancer ASCO Educational Book, January 1, 2008; 2008(1): 49 - 53. [Abstract] [Full Text] [PDF]

				F. Thibault, C. Nos, M. Meunier, C. El Khoury, L. Ollivier, B. Sigal-Zafrani, and K. Clough MRI for Surgical Planning in Patients with Breast Cancer Who Undergo Preoperative Chemotherapy Am. J. Roentgenol., October 1, 2004; 183(4): 1159 - 1168. [Abstract] [Full Text] [PDF]

				M. S. Mano and A. Awada Primary chemotherapy for breast cancer: the evidence and the future Ann. Onc., August 1, 2004; 15(8): 1161 - 1171. [Abstract] [Full Text] [PDF]

				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]

				E. L. Rosen, K. L. Blackwell, J. A. Baker, M. S. Soo, R. C. Bentley, D. Yu, T. V. Samulski, and M. W. Dewhirst Accuracy of MRI in the Detection of Residual Breast Cancer After Neoadjuvant Chemotherapy Am. J. Roentgenol., November 1, 2003; 181(5): 1275 - 1282. [Abstract] [Full Text] [PDF]

				M. Kaufmann, G. von Minckwitz, R. Smith, V. Valero, L. Gianni, W. Eiermann, A. Howell, S. D. Costa, P. Beuzeboc, M. Untch, et al. International Expert Panel on the Use of Primary (Preoperative) Systemic Treatment of Operable Breast Cancer: Review and Recommendations J. Clin. Oncol., July 1, 2003; 21(13): 2600 - 2608. [Abstract] [Full Text] [PDF]

				E. P. Mamounas Ipsilateral Breast Tumor Recurrence After Lumpectomy: Is It Time to Take the Bull by the Horns? J. Clin. Oncol., September 15, 2001; 19(18): 3798 - 3800. [Full Text] [PDF]

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rouzier, R. Articles by Bourstyn, E. Search for Related Content PubMed PubMed Citation Articles by Rouzier, R. Articles by Bourstyn, E. Social Bookmarking                            What's this?