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 Cristofanilli, M. Articles by Hortobagyi, G. N. Search for Related Content PubMed PubMed Citation Articles by Cristofanilli, M. Articles by Hortobagyi, G. N. Social Bookmarking                            What's this?

Invasive Lobular Carcinoma Classic Type: Response to Primary Chemotherapy and Survival Outcomes

From the Departments of Breast Medical Oncology, Pathology, Biostatistics, Surgical Oncology, and Radiotherapy, The University of Texas M.D. Anderson Cancer Center, Houston, TX

Address reprint requests to Massimo Cristofanilli, MD, Department of Breast Medical Oncology, Unit 424, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030-4009; e-mail: mcristof{at}mdanderson.org

	ABSTRACT

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors’ Disclosures of... REFERENCES

 
PURPOSE: To investigate the impact of histologic type invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC) on response to primary chemotherapy (PC) and long-term outcome.

PATIENTS AND METHODS: The study included 1,034 patients with stage II and III breast cancer who participated in six clinical trials of PC at our institution between 1985 and 2002. One hundred twenty-two patients (12%) had ILC and 912 (88%) had IDC. All patients received anthracycline-based PC, and 346 patients (33.5%) also received a taxane as part of PC. Pathologic complete response (pCR) was defined as no evidence of invasive disease in the breast and axillary lymph nodes.

RESULTS: The median patient age was 48 years (range, 18 to 79 years). Patients with ILC tended to be older (median age, 53 years v 47 years for patients with IDC) and have more hormone-receptor–positive tumors (92% v 62%; P < .001), lower nuclear grade (nuclear grade 3, 16% v 56%; P < .001), and higher stage at diagnosis (10% v 0% with stage IIIB or IIIC disease; P < .001). Patients with ILC were less likely to have a pCR (3% v 15%; P < .001) and had a larger number of involved axillary lymph nodes (41% v 26% had > 3 involved nodes; P = .001). At a median follow-up time of 70 months, ILC patients tended to have longer recurrence-free survival (P = .004) and overall survival (P = .001).

CONCLUSION: ILC is characterized by lower rates of pathologic response to PC but better long-term outcomes compared to IDC. pCR might not be a prognostic indicator for this group of patients.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors’ Disclosures of... REFERENCES

 
Invasive lobular carcinoma (ILC) is the second most common type of invasive breast cancer after invasive ductal carcinoma (IDC), and accounts for 5% to 15% of all breast cancer cases.^1-3 Differences in reported incidences of ILC may be due not only to differences in patient populations but also to differences in diagnostic criteria. The classical form of ILC is characterized by small relatively uniform neoplastic cells that invade the stroma singly and in a "single-file" pattern resulting in linear strands.^1,4,5 The cells may encircle the mammary ducts and infiltrate the stroma and adipose tissue without desmoplastic reaction, which makes detection of ILC difficult.^6-9 Differences in clinical behavior between ILC and IDC have been reported. ILCs are more difficult to palpate and visualize mammographically, and have a particular pattern of metastatic spread.^10,11 ILC includes several subtypes: classic, alveolar, solid, tubulo-lobular, signet ring cells, and pleomorphic subtypes.¹² Inactivation of E-cadherin by mutation, loss of heterozygosity, or methylation is considered a characteristic of ILC, particularly the pleomorphic subtype.^13,14 Recently, the use of DNA microarray analysis has allowed identification of a peculiar pattern of gene expression in ILC.^15,16

The prognosis of ILC has been described as equal to or better than that of IDC, but outcome differences are difficult to determine because of the variation in the histologic criteria used to define ILC.^9,17-19 Primary (neoadjuvant) chemotherapy is the standard treatment for patients presenting with locally advanced breast cancer, and its use is extending to earlier stages of disease. Pathologic complete response (pCR) and pathologic nodal status after primary chemotherapy are considered surrogates for survival. We evaluated the impact of histologic type (ILC v IDC) on how likely primary chemotherapy would result in pCR, and on long-term outcome in patients with primary breast cancer.^20-22

	PATIENTS AND METHODS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors’ Disclosures of... REFERENCES

 
Patients
This was a retrospective study of 1,034 patients with primary breast cancer who participated in six trials of primary chemotherapy at The University of Texas M.D. Anderson Cancer Center between 1985 and 2002.^23-26 Inclusion criteria for these trials were untreated stages II and III (T1-3, N0-2, M0) invasive noninflammatory primary breast cancer. All patients had unresected disease and were considered candidates for primary chemotherapy. The Surveillance Committee of The University of Texas M.D. Anderson Cancer Center approved the randomized trials and all participants provided written informed consent before enrollment. In addition, the Committee approved the retrospective review of the medical records for the purposes of this report.

Diagnosis was made by core-needle biopsy of the breast tumor. The histologic type was defined according to the World Health Organization classification.¹ All pathologic specimens were reviewed by breast pathologists at M.D. Anderson Cancer Center. Patients treated during this time whose tumors showed either mixed histologic types or types other than ductal or classic lobular were excluded to allow comparison of the pure lobular and ductal types.

Classic ILC was defined according to the criteria proposed by Fechner.¹² The histologic grade was defined according to the modified Black’s nuclear grading system.²⁷ The estrogen receptor (ER) and progesterone receptor (PR) status of 878 patients, tested by immunohistochemical staining, was available. Staining was performed with standard procedures on 4-µm sections of paraffin-embedded tissues with monoclonal antibodies: 6F11 (Novacastra, Burlingame, CA) for ER, and 1A6 (Novacastra) for PR. Nuclear staining 10% was considered positive.

Treatment
All patients received anthracycline-based primary chemotherapy. One hundred seventy-eight patients (17%) received four cycles of vincristine 1 mg/m², doxorubicin 50 mg/m², and cyclophosphamide 500 mg/m² intravenously (IV) on day 1 and prednisone 100 mg/m² orally on days 1 to 5. Eight hundred fifty-six patients (83%) received four to eight cycles of fluorouracil 500 mg/m² IV on days 1 and 4, doxorubicin 50 mg/m² IV continuous infusion over 72 hours from days 1 to 3, and cyclophosphamide 500 mg/m² IV on day 1. Three hundred thirty-six patients (32%) also received a paclitaxel regimen (175 to 250 mg/m² IV on day 1 every 21 days for four cycles or 80 mg/m² IV on day 1 every week for 12 weeks) as part of primary chemotherapy in randomized clinical trials.^23-26 Breast surgery consisted of segmental mastectomy when tumor size permitted, according to the judgment of the multidisciplinary care team. In other cases, including cases of multifocal disease, mastectomy was performed. Axillary lymph node dissection was performed in 999 patients (97%). Five hundred eighty-two patients (56%) whose hormone receptor status was known to be positive received adjuvant tamoxifen for 5 years. Radiotherapy was delivered at completion of primary chemotherapy, after surgery in all patients treated with lumpectomy, and in patients with locally advanced disease.

Response
pCR was defined as no evidence of invasive carcinoma in the breast and the axillary lymph nodes. Information on the number of positive nodes at surgery was missing for 35 patients because the patient did not undergo surgery (n = 8), because the patient was randomized to a protocol on which she did not undergo nodal dissection (n = 26), or because the patient refused nodal dissection (n = 1). These missing data were not felt to introduce bias because patients with missing data on the number of positive nodes at surgery were not likely to be very different from patients for whom the number of positive nodes at surgery was known. Patients who did not have surgery owing to progressive disease were considered not to have had a pCR.

Statistical Methods
The patient population was described by tabulation of categoric variables and cross-tabulation of the categoric variables with histologic type. ² tests were used to test for an association between categoric variables and histologic type. Continuous variables were described by their minimum, median, and maximum values.

For both pCR and breast complete response (bCR), the number of responses was cross-tabulated by histologic type, and the tables were then stratified by ER and PR status (ER- or PR-positive, or negative for both ER and PR) and by whether or not the patient had received a taxane. Mantel-Haenszel ² tests were performed to test whether there was an association between pCR or bCR and histologic type after adjusting for ER and PR status and after adjusting for taxane use.

The Kaplan-Meier product-limit method was used to assess differences in overall survival and recurrence-free survival between the two histologic types after adjusting for the following: ER/PR status, both ER/PR status and pCR or bCR status, ER/PR status and disease stage, ER/PR status and nuclear grade, and taxane use. The log-rank test and the stratified log-rank test were used to compare survival estimates between histologic types. Overall survival was measured from the date of treatment to the date of death or last follow-up. Recurrence-free survival was measured from the date of treatment to the date of recurrence or last follow-up. Statistical analyses were carried out using SAS 8 (SAS Institute, Cary, NC) and S-Plus 6.1 (Insightful Corporation, Seattle, WA) software.

	RESULTS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors’ Disclosures of... REFERENCES

 
The characteristics of the patients at diagnosis are summarized in Table 1. The median patient age was 48 years (range, 18 to 79 years). One hundred twenty-two patients (12%) had ILC, and 912 (88%) had IDC. The median follow-up time was 70 months.

Patients with ILC were more likely to receive taxanes as part of primary chemotherapy (taxanes use, 46% v 32%; P = .002), in part because the more advanced stage of the tumors at presentation necessitated patients’ participation in protocols for locally advanced disease.

Nine hundred ninety-eight patients (97%) had adequate response after primary chemotherapy and proceeded to surgery. Two hundred thirty-eight patients (27%) were treated with breast-conserving therapy (BCT). Patients with ILC were more likely than those with IDC to undergo mastectomy (83% v 67%; P = .003). The proportion of patients who underwent BCT was significantly lower for patients with ILC (16%) than for those with IDC (29%; P = .003). ILC was an independent predictor of ineligibility for BCT.

One hundred forty-two patients (14%) had a pCR (Tables 2 and 3). ILC was associated with a lower pCR rate (3% v 15%; P < .001) and a higher incidence of residual lymph node disease ( four positive lymph nodes, 41% v 26%; P = .001). In four patients, the pCR status differed from the bCR status (Table 4). One patient had two positive nodes and in situ disease and thus did not have a pCR but did have a bCR. Three patients had no residual disease or in situ residual disease but had an unknown number of positive nodes. These patients had an unknown pCR status but did have a bCR.

View larger version (12K): [in this window] [in a new window]   Fig 1. Recurrence-free survival by histologic type.

View larger version (11K): [in this window] [in a new window]   Fig 2. Overall survival by histologic type.

View larger version (12K): [in this window] [in a new window]   Fig 3. Recurrence-free survival by histologic type for patients with estrogen-receptor (ER) or progesterone-receptor (PR) –positive disease.

View larger version (11K): [in this window] [in a new window]   Fig 4. Overall survival by histologic type for patients with estrogen-receptor (ER) or progesterone-receptor (PR) –positive disease.

View larger version (18K): [in this window] [in a new window]   Fig 5. Recurrence-free survival by histologic type and pathologic complete response (Path CR) status for patients with estrogen-receptor (ER) or progesterone-receptor (PR) –positive disease.

View larger version (17K): [in this window] [in a new window]   Fig 6. Overall survival by histologic type and pathologic complete response (Path CR) status for patients with estrogen-receptor (ER) or progesterone-receptor (PR) –positive disease.

	DISCUSSION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors’ Disclosures of... REFERENCES

 
The management of primary breast cancer has changed over the years, and primary chemotherapy is used more frequently now than in the past. Primary chemotherapy downstages tumors, but more importantly, it permits in vivo assessment of tumor response and consequently provides an opportunity to predict outcome and tailor therapy.^28,29 Moreover, breast cancer’s response to primary chemotherapy can be used to evaluate biologic marker expression, and serial modifications during therapy provide an additional tool to predict chemosensitivity. Clinical and pathologic responses to primary chemotherapy correlate with prognosis, and pCR is considered a surrogate for OS.^20,30,31

Our results indicate that classic ILC responds less frequently to primary chemotherapy. More importantly, the difference in pCR rate between ILC and IDC persisted even after adjusting for hormone-receptor status and use of taxanes. A positive hormone-receptor status has previously been associated with a lower chance of pathologic response to primary chemotherapy. In a recent retrospective study of 1,018 patients, Buzdar et al³² found that rates of pCR to primary chemotherapy were significantly higher in patients with ER-negative tumors (P < .001). Conversely, the addition of taxanes, particularly in sequential regimens, has been shown to translate into higher pathologic response rates.^20,33-35

We found that patients with ILC were more likely than patients with IDC to be treated electively with mastectomy, and because of the diffuse nature of the disease, and the poorer response to chemotherapy, these patients were rarely candidates for breast-conserving surgery. This finding has previously been reported by Cocquyt et al.³⁶ The authors reviewed 135 patients treated with primary chemotherapy and found that BCT was possible in 50% of patients with IDC and 35% of patients with ILC. This is important because BCT is currently the primary end point for patients with early breast cancer undergoing primary chemotherapy^20,33,37 and our findings indicate that there is no such benefit for patients with ILC.

The most striking finding of our investigation was that despite more advanced disease at presentation and the low pCR rate, and after adjusting for the imbalances in hormone-receptor–positive disease, patients with ILC had a better long-term outcome than did patients with IDC. ILC has repeatedly been shown to be associated with better long-term outcome than IDC.^8-10 Several epidemiologic factors may explain the correlation. Women with ILC are usually older, are more likely to have previously used hormone-replacement therapy, and are more likely to have hormone-receptor–positive disease.^18,38 In previous studies of primary chemotherapy, reported rates of ILC included in primary chemotherapy studies were 7% v 12%,^38,39 but differences in outcome based in histologic subset analysis were not done.

To our knowledge, this is the first report that addresses the correlation between histologic type and response to primary chemotherapy in such a large cohort of patients, as a measure of chemo-sensitivity and long-term outcome. Our study indicated that very few patients with ILC achieve a pCR to primary chemotherapy and that pCR to primary chemotherapy in ILC may have no prognostic significance. Overall, these results indicate that the role of primary chemotherapy in ILC should be reconsidered. Primary chemotherapy in this subgroup does not achieve the two main objectives of this treatment: adequate downstaging of disease to allow for BCT and provision of a surrogate marker of prognosis (pCR).

The results also indicate that the use of primary systemic therapy in women with ILC should be restricted to patients with inoperable disease and should be more tailored to the peculiar biologic features of the disease. For example, primary endocrine treatments should be explored as a possible, more effective treatment for ILC. Initial studies of tamoxifen in the primary setting showed that this is a good alternative option for elderly patients who are poor candidates for primary cytotoxic chemotherapy.⁴⁰ Subsequent studies in postmenopausal patients with ER-positive tumors demonstrated the effectiveness of aromatase inhibitors as primary therapy despite the rarity of pCR.^41-43 More recently, a comparison between tamoxifen and anastrozole revealed a higher rate of BCT in the anastrozole group.⁴⁴

Other scientific approaches, such as genomics and proteomics, may answer questions regarding biologic behavior and chemosensitivity and assist in the selection of the most appropriate therapy. Small series have demonstrated that microarray analysis can separate tumors into four groups according to proliferation, ER, c-erbB-2, and apoptosis genes.¹⁵ A recent report showed that specific changes in gene expression distinguished lobular and ductal carcinomas.¹⁶

In conclusion, our study indicates that primary cytotoxic chemotherapy may not be the best standard of care for women with ILC. The use of primary endocrine therapy in women with inoperable ILC should be investigated. Additional investigation, including genomic and proteomic studies, are warranted to help clarify the unique biologic features of this disease.

	Authors’ Disclosures of Potential Conflicts of Interest

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors’ Disclosures of... REFERENCES

 
The authors indicated no potential conflicts of interest.

	Acknowledgment

 
We thank Dr Donald A. Berry for statistical review and insightful comments.

	NOTES

 
Supported by the Nellie B. Connally Breast Cancer Research Fund and the Susan G. Komen Fellowship Fund.

Authors’ disclosures of potential conflicts of interest are found at the end of this article.

	REFERENCES

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors’ Disclosures of... REFERENCES

 
1. The World Health Organization: The World Health Organization histological typing of breast tumors second edition. Am J Clin Pathol 78:806-816, 1982[Medline]

2. Wellings SR, Jensen HM, Marcum RG: An atlas of subgross pathology of the human breast with special reference to possible precancerous lesions. J Natl Cancer Inst 55:231-273, 1975

3. Fisher ER, Gregorio RM, Fisher B, et al: The pathology of invasive breast cancer: A syllabus derived from findings of the National Surgical Adjuvant Breast Project (protocol No. 4). Cancer 36:1-85, 1975[CrossRef][Medline]

4. Wheeler JE, Enterline HT: Lobular carcinoma of the breast in situ and infiltrating. Pathol Annu 11:161-188, 1976[Medline]

5. Martinez V, Azzopardi JG: Invasive lobular carcinoma of the breast: Incidence and variants. Histopathology 3:467-488, 1979[Medline]

6. Foote FWJ, Stewart FW: Histologic classification of carcinoma of the breast. Surgery 19:74-99, 1946

7. Dixon JM, Anderson TJ, Page DL, et al: Infiltrating lobular carcinoma of the breast. Histopathology 6:149-161, 1982[Medline]

8. du Toit RS, Locker AP, Ellis IO, et al: Invasive lobular carcinomas of the breast: The prognosis of histopathological subtypes. Br J Cancer 60:605-609, 1989[Medline]

9. Sastre-Garau X, Jouve M, Asselain B, et al: Infiltrating lobular carcinoma of the breast: Clinicopathologic analysis of 975 cases with reference to data on conservative therapy and metastatic patterns. Cancer 77:113-120, 1996[CrossRef][Medline]

10. Harris M, Howell A, Chrissohou M, et al: A comparison of the metastatic pattern of infiltrating lobular carcinoma and infiltrating duct carcinoma of the breast. Br J Cancer 50:23-30, 1984[Medline]

11. Lamovec J, Bracko M: Metastatic pattern of infiltrating lobular carcinoma of the breast: An autopsy study. J Surg Oncol 48:28-33, 1991[Medline]

12. Fechner RE: Histologic variants of infiltrating lobular carcinoma of the breast. Hum Pathol 6:373-378, 1975[Medline]

13. Cleton-Jansen AM: E-cadherin and loss of heterozygosity at chromosome 16 in breast carcinogenesis: Different genetic pathways in ductal and lobular breast cancer? Breast Cancer Res 4:5-8, 2002[Medline]

14. de Leeuw WJ, Berx G, Vos CB, et al: Simultaneous loss of E-cadherin and catenins in invasive lobular breast cancer and lobular carcinoma in situ. J Pathol 183:404-411, 1997[CrossRef][Medline]

15. Sorlie T, Perou CM, Tibshirani R, et al: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 98:10869-10874, 2001[Abstract/Free Full Text]

16. Korkola JE, DeVries S, Fridlyand J, et al: Differentiation of lobular versus ductal breast carcinomas by expression microarray analysis. Cancer Res 63:7167-7175, 2003[Abstract/Free Full Text]

17. Silverstein MJ, Waisman JR, Gamagami P, et al: Intraductal carcinoma of the breast (208 cases): Clinical factors influencing treatment choice. Cancer 66:102-108, 1990[CrossRef][Medline]

18. Toikkanen S, Pylkkanen L, Joensuu H: Invasive lobular carcinoma of the breast has better short- and long-term survival than invasive ductal carcinoma. Br J Cancer 76:1234-1240, 1997[Medline]

19. Rouzier RD, Youmsi E, Delaloge S, et al: Predictors of breast-conserving surgery after epirubicin-based neoadjuvant chemotherapy for large breast carcinoma. Proc Am Soc Clin Oncol 22:38a, 2003 (abstr 151)

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

21. Rouzier R, Extra JM, Klijanienko J, et al: Incidence and prognostic significance of complete axillary downstaging after primary chemotherapy in breast cancer patients with T1 to T3 tumors and cytologically proven axillary metastatic lymph nodes. J Clin Oncol 20:1304-1310, 2002[Abstract/Free Full Text]

22. Kuerer HM, Newman LA, Smith TL, et al: Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol 17:460-469, 1999[Abstract/Free Full Text]

23. Buzdar AU, Singletary SE, Theriault RL, et al: Prospective evaluation of paclitaxel versus combination chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide as neoadjuvant therapy in patients with operable breast cancer. J Clin Oncol 17:3412-3417, 1999[Abstract/Free Full Text]

24. Green MC, Buzdar AU, Smith T, et al: Weekly paclitaxel followed by FAC in the neo-adjuvant setting provides improved pathologic complete remission rates compared to standard paclitaxel followed by FAC therapy-preliminary results of an ongoing prospective randomized trial. Proc Am Soc Clin Oncol 20:33a, 2001 (abstr 129)

25. Dhingra K, Esparza-Guerra L, Valero V, et al: A phase III randomized trial of dose-intensive neoadjuvant 5FU, doxorubicin, cyclophosphamide (FAC) with G-CSF (filgrastin) in locally advanced breast cancer (LABC): Efficacy and safety data. Proc Amer Soc Clin Oncol 18:74a, 1999 (abstr 278)

26. Hortobagyi GN, Holmes FA, Frye D, et al: Comparison of two adjuvant chemotherapy programs for locally advanced breast cancer: A prospective randomized trial. Proc Am Soc Clin Oncol 9:21, 1990 (abstr 77)

27. Black MM, Speer FD: Nuclear structure in cancer tissues. Surg Gynecol Obstet 105:97-102, 1957[Medline]

28. Valero V, Buzdar AU, McNeese M, et al: Primary chemotherapy in the treatment of breast cancer: The University of Texas M.D. Anderson Cancer Center experience. Clin Breast Cancer 3:S63-S68, 2002 (suppl 2)

29. Kaufmann M, von Minckwitz G, Smith R, et al: International expert panel on the use of primary (preoperative) systemic treatment of operable breast cancer: Review and recommendations. J Clin Oncol 21:2600-2608, 2003[Abstract/Free Full Text]

30. Hortobagyi GN, Ames FC, Buzdar AU, et al: Management of stage III primary breast cancer with primary chemotherapy, surgery, and radiation therapy. Cancer 62:2507-2516, 1988[CrossRef][Medline]

31. 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]

32. Buzdar AU, Valero V, Theriault RL, et al: Pathologic complete response to chemotherapy is related with hormone receptor status. Breast Cancer Res Treat 82:S69a, 2003 (suppl 1)

33. Makris A, Powles TJ, Ashley SE, 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]

34. Hutcheon AW, Heys SD, Sarkar TK: Neoadjuvant docetaxel in locally advanced breast cancer. Breast Cancer Res Treat 79:S19-S24, 2003 (suppl 1)

35. Bear HD, Anderson S, Brown A, et al: The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: Preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 21:4165-4174, 2003[Abstract/Free Full Text]

36. Cocquyt VF, Blondeel PN, Depypere HT, et al: Different responses to preoperative chemotherapy for invasive lobular and invasive ductal breast carcinoma. Eur J Surg Oncol 29:361-367, 2003[CrossRef][Medline]

37. Bonadonna G, Veronesi U, Brambilla C, et al: Primary chemotherapy to avoid mastectomy in tumors with diameters of three centimeters or more. J Natl Cancer Inst 82:1539-1545, 1990[Abstract/Free Full Text]

38. MacGrogan G, Mauriac L, Durand M, et al: Primary chemotherapy in breast invasive carcinoma: Predictive value of the immunohistochemical detection of hormonal receptors, p53, c-erbB-2, MiB1, pS2 and GST pi. Br J Cancer 74:1458-1465, 1996[Medline]

39. Calais G, Berger C, Descamps P, et al: Conservative treatment feasibility with induction chemotherapy, surgery, and radiotherapy for patients with breast carcinoma larger than 3 cm. Cancer 74:1283-1288, 1994[CrossRef][Medline]

40. Horobin JM, Preece PE, Dewar JA, et al: Long-term follow-up of elderly patients with locoregional breast cancer treated with tamoxifen only. Br J Surg 78:213-217, 1991[Medline]

41. Dixon JM, Renshaw L, Bellamy C, et al: The effects of neoadjuvant anastrozole (Arimidex) on tumor volume in postmenopausal women with breast cancer: A randomized, double-blind, single-center study. Clin Cancer Res 6:2229-2235, 2000[Abstract/Free Full Text]

42. Dixon JM, Love CDB, Bellamy COC, et al: Letrozole as primary medical therapy for locally advanced and large operable breast cancer. Breast Cancer Res Treat 66:191-199, 2001[CrossRef][Medline]

43. Eiermann W, Paepke S, Appfelstaedt J, et al: Preoperative treatment of postmenopausal breast cancer patients with letrozole: A randomized double-blind multicenter study. Ann Oncol 12:1527-1532, 2001[Abstract/Free Full Text]

44. Smith I, Dowsett M, on behalf of the IMPACT trialists: Comparison of anastrozole vs. tamoxifen alone and in combination as neoadjuvant treatment of estrogen receptor-positive breast cancer in postmenopausal women: The IMPACT trial. Breast Cancer Res Treat 82:S5, 2003 (suppl 1)

Submitted March 15, 2004; accepted October 5, 2004.

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

This article has been cited by other articles:

				J. P. Breyer, M. E. Sanders, D. C. Airey, Q. Cai, B. L. Yaspan, P. A. Schuyler, Q. Dai, F. Boulos, M. G. Olivares, K. M. Bradley, et al. Heritable Variation of ERBB2 and Breast Cancer Risk Cancer Epidemiol. Biomarkers Prev., April 1, 2009; 18(4): 1252 - 1258. [Abstract] [Full Text] [PDF]

				B. C. Pestalozzi, D. Zahrieh, E. Mallon, B. A. Gusterson, K. N. Price, R. D. Gelber, S. B. Holmberg, J. Lindtner, R. Snyder, B. Thurlimann, et al. Distinct Clinical and Prognostic Features of Infiltrating Lobular Carcinoma of the Breast: Combined Results of 15 International Breast Cancer Study Group Clinical Trials J. Clin. Oncol., June 20, 2008; 26(18): 3006 - 3014. [Abstract] [Full Text] [PDF]

				M. Kaufmann, G. von Minckwitz, H. D. Bear, A. Buzdar, P. McGale, H. Bonnefoi, M. Colleoni, C. Denkert, W. Eiermann, R. Jackesz, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: new perspectives 2006 Ann. Onc., December 1, 2007; 18(12): 1927 - 1934. [Abstract] [Full Text] [PDF]

				N. Biglia, L. Mariani, L. Sgro, P. Mininanni, G. Moggio, and P. Sismondi Increased incidence of lobular breast cancer in women treated with hormone replacement therapy: implications for diagnosis, surgical and medical treatment Endocr. Relat. Cancer, September 1, 2007; 14(3): 549 - 567. [Abstract] [Full Text] [PDF]

				O Camara, M Rengsberger, A Egbe, A Koch, M Gajda, U Hammer, C Jorke, C Rabenstein, M Untch, and K Pachmann The relevance of circulating epithelial tumor cells (CETC) for therapy monitoring during neoadjuvant (primary systemic) chemotherapy in breast cancer Ann. Onc., September 1, 2007; 18(9): 1484 - 1492. [Abstract] [Full Text] [PDF]

				C. Shimizu, M. Ando, T. Kouno, N. Katsumata, and Y. Fujiwara Current Trends and Controversies over Pre-operative Chemotherapy for Women with Operable Breast Cancer Jpn. J. Clin. Oncol., January 3, 2007; (2007) hyl122v1. [Abstract] [Full Text] [PDF]

				J. S. Reis-Filho, P. T. Simpson, N. C. Turner, M. B. Lambros, C. Jones, A. Mackay, A. Grigoriadis, D. Sarrio, K. Savage, T. Dexter, et al. FGFR1 Emerges as a Potential Therapeutic Target for Lobular Breast Carcinomas. Clin. Cancer Res., November 15, 2006; 12(22): 6652 - 6662. [Abstract] [Full Text] [PDF]

				B. D. Smith, B. G. Haffty, A. Hurria, D. H. Galusha, and C. P. Gross Postmastectomy Radiation and Survival in Older Women With Breast Cancer J. Clin. Oncol., October 20, 2006; 24(30): 4901 - 4907. [Abstract] [Full Text] [PDF]

				A. Bottini, D. Generali, M. P. Brizzi, S. B. Fox, A. Bersiga, S. Bonardi, G. Allevi, S. Aguggini, G. Bodini, M. Milani, et al. Randomized Phase II Trial of Letrozole and Letrozole Plus Low-Dose Metronomic Oral Cyclophosphamide As Primary Systemic Treatment in Elderly Breast Cancer Patients J. Clin. Oncol., August 1, 2006; 24(22): 3623 - 3628. [Abstract] [Full Text] [PDF]

				M. Tubiana-Hulin, D. Stevens, S. Lasry, J. M. Guinebretiere, L. Bouita, C. Cohen-Solal, P. Cherel, and J. Rouesse Response to neoadjuvant chemotherapy in lobular and ductal breast carcinomas: a retrospective study on 860 patients from one institution Ann. Onc., August 1, 2006; 17(8): 1228 - 1233. [Abstract] [Full Text] [PDF]

				I. Sachelarie, M. L. Grossbard, M. Chadha, S. Feldman, M. Ghesani, and R. H. Blum Primary Systemic Therapy of Breast Cancer Oncologist, June 1, 2006; 11(6): 574 - 589. [Abstract] [Full Text] [PDF]

				M. Kaufmann, G. N. Hortobagyi, A. Goldhirsch, S. Scholl, A. Makris, P. Valagussa, J.-U. Blohmer, W. Eiermann, R. Jackesz, W. Jonat, et al. Recommendations From an International Expert Panel on the Use of Neoadjuvant (Primary) Systemic Treatment of Operable Breast Cancer: An Update J. Clin. Oncol., April 20, 2006; 24(12): 1940 - 1949. [Abstract] [Full Text] [PDF]

				A. Katz Does Neoadjuvant/Adjuvant Chemotherapy Change the Natural History of Classic Invasive Lobular Carcinoma? J. Clin. Oncol., September 20, 2005; 23(27): 6796 - 6796. [Full Text] [PDF]

				M. Cristofanilli, A. Gonzalez-Angulo, and G. Hortobagyi In Reply: J. Clin. Oncol., September 20, 2005; 23(27): 6796 - 6797. [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 Cristofanilli, M. Articles by Hortobagyi, G. N. Search for Related Content PubMed PubMed Citation Articles by Cristofanilli, M. Articles by Hortobagyi, G. N. Social Bookmarking                            What's this?