p53 Mutation and MDR1 Overexpression in Local and Distant Failures of Breast Cancer Treated by Lumpectomy and Radiation
Abstract
To search for the risk factors associated with local recurrence and distant metastasis of breast cancer treated by lumpectomy and irradiation, 112 cases treated during a period of eleven years (1983-1994) at University Hospital, Jacksonville were studied. Among those studied, 4(4%) patien ts recurred locally within one year of treatment; 10 (9%) cases presented with distant metastasis within 3 years. No obvious clinical risk factors were identified for local recurrence, however, positive node status appeared to be associated with distant metastasis. The primary tumors of these cases were then studied using immnohisto che mical staining to evaluate the potential prognostic value of tumor markers including estrogen receptor (ER), progesterone receptor(PR), tumor suppressor gene p53, HER 2/ neu oncogene and multidrug resistance gene (MDR1). The overexpression of p53 was associated with all local recurrence while 50 per cent was associated with distant failures. The overexpression of MDRI gene was observed in 80 per cent of all distant failure cases. This interesting findings may warrant further studies on a larger scale to assess the predictive value of p53 and MDRI in the overall management of breast cancer.
References
1. Blichert-Toft M, Brincker H, Anderson J, et al. A Danish randomized trial comparing breast preserving therapy with mastectomy in mammary carcinoma. Acta Oncol 1988;27:671.
2. Srrazin D, Le M, Arriagada R, et al. Ten-year results of a randomized trial comparing a conservartive treatment to mastectomy in early breast cancer. Radiother Oncol 1989;14:177.
3. Valagussa P, Bonadonna G, Veronesi U. Patterns of relapse and survival following radical mastectomy: analysis of 716 consecutive patients. Cancer 1978; 41:1170.
4. Fisher B, Wolmark N, Bauer M, et al. The accuracy of clinical nodal staging and of limited axillary dissection as a determinant of histologic nodal status in carcinoma of the breast. Surg Gynecol Obstet 1981; 152:765.
5. Early Breast Cancer Trialists' Group. Treatment of early breast cancer: world-wide experience, 1985-1990, vol 1. Oxford, U.K.: Oxford University, 1990.
6. Rutgvist L, Pettersson D, Johansson H. Adjuvant radiation therapy versus surgery alone in operable breast cancer: long-term follow-up in a randomized clinical trial. Radiother Oncol 1993; 26:104.
7. Van Dongen J, Bartelink H, Fentimen I, et al, Randomized clinical trial to assess the value of breast-conserving therapy in stage I and Il breast cancer, EORTC 10801 trial. J Natl Cancer Inst Monogr 1992: 11:15.
8. Lichter A, Lippman M, Danforth D, et al. Mastectomy versus breast conserving therapy in the treatment of stage I and II carcinoma of the breast: a randomized trial at the National Cancer Institute. J Clin Oncol 1992; 10:976.
9.Fisher B, Anderson S, Redmond C, et al, Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with and without irradiation in the treatment of breast cancer. N Engl J Med 1995: 333:1456.
10. Fisher B, Redmond C, and others of the National Surgical Adjuvant Breast and Bowel Project. Lumpectomy for breast cancer; an update of the NSABP experience. J Natl Cancer Inst Monogr 1992: 11:7.
11. Fisher B, Constantino J, Redmond C, et al. Lumpectomy compared with lumpectomy and radiation therapy for the treatment of intraductal breast cancer. N Engl J Med 1993; 328:1581.
12. Fowble B, Solin L, Schultz D, et al. Frequency sites of relapse, and outcome of regional node failures following surgery and radiation for early breast cancer. Int J Radiat Oncol Biol Phys 1989; 17:703.
13, Rosen P, Groshen S, Saigo P, et al. A long-term follow-up study of survival in stage I (T1 NOMO) and stage II (TIN1MO) breast carcinoma. J Clin Oncol 1989: 7:355.
14. Borger J, Kemperman H, Hart A, et al. Risk factors in breast-conservation therapy. J Clin Oncol 1994; 12:653.
15. Bonadonna G, Valagussa P, Rossi A, et al. Ten-year experience with CMF-based adjuvant chemotherapy in resectable breast cancer. Breast Cancer Res Treat 1985; 5:95.
16. Fisher B, Fisher E, Remond C, Ten year results from the NSABP clinical trial evaluating the use of L-phenylalanine mustard (LPAM) in the management of primary breast cancer. JClin Oncol 1986; 4:929.
17. Howell A, George W, Crowther D, et al. Controlled trial of adjuvant chemotherapy with cyclophosphamide, methotrexate, and fluorouracil for breast cancer. Lancet 1984; 2:307.
18. Rubens R, Knight R, Fentiman I, et al. Controlled trial of adjuvant chemotherapy with melphalan for breast cancer. Lancet 1983; 1:839.
19. Muss H, Cooper R, Brockschmidt J, et al. A randomized trial of adjuvant chemotherapy (CT) without radiation therapy (RT) for stage ll breast cancer: 11-year follow-up of Piedmont Oncology Association protocol 74176. Breast Cancer Res Treat 1989; 14:185.
20. McArdle C, Crawford D, Dykes E, et al. Adjuvant radio- therapy and chemotherapy in breast cancer. Br J Surg 1986;73:264.
21. Blomqvist C, Tiusanen K, Elomma l, et al. The combination of radiotherapy, Chemotherapy adjuvant (cyclophosphamide-doxorubicin-ftorafur) and tamoxifen in stage II breast cancer; long-term results of a randomized trial. Br J Cancer 1992;66:1171.
22. Bonadonna G, Valagussa P, Zucali R, et al. Feasibility of adjuvant chemotherapy plus radiotherapy in operable breast cancer. In: Harris JR, Hellman S, Silen W, eds. Con- servative management of breast cancer. Philadelphia: JB Lippincott,1983:329.
23. Rutqvist L, Cedermark B, Fornander T, et al. The relationship between hormone receptor content and the effect of adjuvant tamoxifen in operable breast cancer. JClin Oncol 1989;7:1474.
24. Nolvadex Adjuvant Trial Organization. Controlled trial of tamo-xifen as a single adjuvant agent in management of early breast cancer: Analysis at six years by the Nolvadex Adjuvant trial Organization. Lancet 1985; 1:836.
25. Wazer D, Joyce M,Chan W, et al. Effects of tamoxifen on the radiosensitivity of hormonally responsive and unresponsive breast carcinoma cells. Radiat Oncol Invest 1993; 1:20.
26. Margolese R. Surgical considerations in selecting local therapy cancer: analysis at six years by the Nolvadex Adjuvant Trial Organization, Lancet 1985; 1:836.
27. Breast Cancer Trials Committee. Scottish Cancer Trials Office; Adjuvant tamoxifen in the management of operable breast cancer: the Scottish trial. Lancet 1987; 2:171.
28. Veronesi U, Luini A, Galimberti V, et al. Conservation approaches for the management of stage l/ll carcinoma of the breast: Milan Cancer Institute Trials, World J Surg 1994;18:70.
29, Vilcoq J, Calle R, Stacey p, et al. The outcome of treatment by tumorectomy and radiotherapy of patients with operable breast cancer. Int J Radiat Oncol Biol Phys 1981;7:1327.
30. Boyages J, Recht A, Connolly J, et al. Early breast cancer: predictors of breaist recurrence for patients treated with conservative surgery and radiation therapy. Radiother Oncol 1990; 19:29.
31. Kurtz J,Spitalier J, Amalric R, et al. Mammary recurrence in women younger than forty. Int J Radiat Oncol Biol Phys 1988;15:271.
32. Matthews R, McNeese M, Montague E, et al. Prognostic implications of age in breast cancer patients treated with tumorectomy and irradiation or with mastectomy. Int J Radiat Oncol Biol Phys 1988; 14:659.
33. Haffty B, Fischer D, Rose M, et al. Prognostic factors for local recurrence in the conservatively trearted breast cancer patient: a cautious interpretation of the data. J Clin Oncol 1991:9:997.
34. Rutqvist L, Pettersson D, Johansson H, Adjuvant radiation therapy versus surgery alone in operable breast cancer: long-term follow-up in a randomized clinical trial. Radiother Oncol 1993:26:104.
35. McGuire WL. Breast cancer prognostic factors: evaluation guide-lines. J Natl Cancer Inst 1990; 83:154.
36. Clark G. Prognostic and predictive factors. In: Harris J, Lippman M, Morrow M, et al. Diseases of the Breast. Philadelphia: Lippincott-Raven, 1996.
37. FoxS, Smith K, Hollyer J, et al. The epidermal growth factor receptor as a prognostic marker: results of 370 patients and review of 3009 patients. Breast Cancer Res Treat 1994; 29:41.
38. Rosen P, Lesser M, Arroyo C. p53 in node-negative breast carcinoma: an immunohistochemical study of epidemiologic risk factors, histologic features, and prognosis. J Clin Oncol 1995: 13:821.
39. Thor AD, Moore II, DH, Edgerton DM, et al, Accumulation of p53 Tumor suppressor gene protein: AnIndependent Marker of Prognosis in Breast Cancers. J Natl Cancer Inst 1992; 84:845-5.
40. Andersen J, Thorpe S, King W, et al. The prognostic value of immunohistochemical estrogen receptor analysis in paraffin-embedded and frozen sections versus that of steroid-binding assays. Eur J Cancer 1990: 26:442.
41. Muss H, Thor A, Berry D, et al. c-erbB-2 Expression and response to adjuvant therapy in women with node-positive early breast cancer. N Engl J Med 1994; 330:1260.
42. Prosser J, Thompson AM, Cranston G, et al. Evidence that p53 behaves as a tumor suppressor gene in sporadic breast tumors. Oncogene 1990; 5:1573-9.
43. Malkin D, Li FP, Strong LC, et al. Germ line p53 mutations in a familial syndrome of breast cancer. Science 1990; 250: 1233-8.
44. Trock BJ, Leonessa F,Clarke R. Multidrug resistance in breast cancer: a Meta-analysis of MR1/GP 170 Expression and its possible functional significance. J Natl Cancer Inst 1997;89:917-31.
45. Sanflippo O, Ronchi E, de Marco C, di Fronzo G, Silvestini R. Expression of P-glycoprotein in breast cancer tissue and in vitro resistance ot doxorubicin and vincristine. Eur J Cancer 1991: 27:155-8
46. Kim R. Expression of the multidrug resistance gene in human tumors. Hiroshima J Med Science 1990; 39:71-7.
47. Dixon AR, Bell F, Ellis IO, Elston CW, Blamey RW, P-glycoprotein expression in locally advanced breast cancer treated by neoadjuvant chemotherapy.BrJCancer 1992;66:537-41.
48. Prempree T, Amornmarn R, Nguyen TQ, Arce C, Failace W. Chomosome aberrations, p53 gene mutations and MDR1 amplification in Glioblastoma Multiforme. Presented at Siriraj Scientific Congress, Siriraj Hospital, Bangkok, March 1999:8-12.
49. Shapiro JR, Shapiro WR. Therapy modifies cellular heterogeneity in human malignant glioma. Acvances in Oncology 1994;8:21-9.
50. O'Shanghnessy JA, Cowan KH. Current status of Paclitaxel in the treatment of breast cancer. Breast Cancer Res Treat 1995; 33:27-37.
51. Fugua SAW. Estrogen Receptor Mutagenesis and hormone resistance. Cancer 1994; 74:1026-9.
52. Rozan S, Vincent Salomon A, Zafani B, et al. No significant predictive value of c-erbB2 or p53 expression regarding sensitivityto primarychemotherapyorradiotherapyinbreast cancer. Int J Cancer 1998; 79:27-33.
2. Srrazin D, Le M, Arriagada R, et al. Ten-year results of a randomized trial comparing a conservartive treatment to mastectomy in early breast cancer. Radiother Oncol 1989;14:177.
3. Valagussa P, Bonadonna G, Veronesi U. Patterns of relapse and survival following radical mastectomy: analysis of 716 consecutive patients. Cancer 1978; 41:1170.
4. Fisher B, Wolmark N, Bauer M, et al. The accuracy of clinical nodal staging and of limited axillary dissection as a determinant of histologic nodal status in carcinoma of the breast. Surg Gynecol Obstet 1981; 152:765.
5. Early Breast Cancer Trialists' Group. Treatment of early breast cancer: world-wide experience, 1985-1990, vol 1. Oxford, U.K.: Oxford University, 1990.
6. Rutgvist L, Pettersson D, Johansson H. Adjuvant radiation therapy versus surgery alone in operable breast cancer: long-term follow-up in a randomized clinical trial. Radiother Oncol 1993; 26:104.
7. Van Dongen J, Bartelink H, Fentimen I, et al, Randomized clinical trial to assess the value of breast-conserving therapy in stage I and Il breast cancer, EORTC 10801 trial. J Natl Cancer Inst Monogr 1992: 11:15.
8. Lichter A, Lippman M, Danforth D, et al. Mastectomy versus breast conserving therapy in the treatment of stage I and II carcinoma of the breast: a randomized trial at the National Cancer Institute. J Clin Oncol 1992; 10:976.
9.Fisher B, Anderson S, Redmond C, et al, Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with and without irradiation in the treatment of breast cancer. N Engl J Med 1995: 333:1456.
10. Fisher B, Redmond C, and others of the National Surgical Adjuvant Breast and Bowel Project. Lumpectomy for breast cancer; an update of the NSABP experience. J Natl Cancer Inst Monogr 1992: 11:7.
11. Fisher B, Constantino J, Redmond C, et al. Lumpectomy compared with lumpectomy and radiation therapy for the treatment of intraductal breast cancer. N Engl J Med 1993; 328:1581.
12. Fowble B, Solin L, Schultz D, et al. Frequency sites of relapse, and outcome of regional node failures following surgery and radiation for early breast cancer. Int J Radiat Oncol Biol Phys 1989; 17:703.
13, Rosen P, Groshen S, Saigo P, et al. A long-term follow-up study of survival in stage I (T1 NOMO) and stage II (TIN1MO) breast carcinoma. J Clin Oncol 1989: 7:355.
14. Borger J, Kemperman H, Hart A, et al. Risk factors in breast-conservation therapy. J Clin Oncol 1994; 12:653.
15. Bonadonna G, Valagussa P, Rossi A, et al. Ten-year experience with CMF-based adjuvant chemotherapy in resectable breast cancer. Breast Cancer Res Treat 1985; 5:95.
16. Fisher B, Fisher E, Remond C, Ten year results from the NSABP clinical trial evaluating the use of L-phenylalanine mustard (LPAM) in the management of primary breast cancer. JClin Oncol 1986; 4:929.
17. Howell A, George W, Crowther D, et al. Controlled trial of adjuvant chemotherapy with cyclophosphamide, methotrexate, and fluorouracil for breast cancer. Lancet 1984; 2:307.
18. Rubens R, Knight R, Fentiman I, et al. Controlled trial of adjuvant chemotherapy with melphalan for breast cancer. Lancet 1983; 1:839.
19. Muss H, Cooper R, Brockschmidt J, et al. A randomized trial of adjuvant chemotherapy (CT) without radiation therapy (RT) for stage ll breast cancer: 11-year follow-up of Piedmont Oncology Association protocol 74176. Breast Cancer Res Treat 1989; 14:185.
20. McArdle C, Crawford D, Dykes E, et al. Adjuvant radio- therapy and chemotherapy in breast cancer. Br J Surg 1986;73:264.
21. Blomqvist C, Tiusanen K, Elomma l, et al. The combination of radiotherapy, Chemotherapy adjuvant (cyclophosphamide-doxorubicin-ftorafur) and tamoxifen in stage II breast cancer; long-term results of a randomized trial. Br J Cancer 1992;66:1171.
22. Bonadonna G, Valagussa P, Zucali R, et al. Feasibility of adjuvant chemotherapy plus radiotherapy in operable breast cancer. In: Harris JR, Hellman S, Silen W, eds. Con- servative management of breast cancer. Philadelphia: JB Lippincott,1983:329.
23. Rutqvist L, Cedermark B, Fornander T, et al. The relationship between hormone receptor content and the effect of adjuvant tamoxifen in operable breast cancer. JClin Oncol 1989;7:1474.
24. Nolvadex Adjuvant Trial Organization. Controlled trial of tamo-xifen as a single adjuvant agent in management of early breast cancer: Analysis at six years by the Nolvadex Adjuvant trial Organization. Lancet 1985; 1:836.
25. Wazer D, Joyce M,Chan W, et al. Effects of tamoxifen on the radiosensitivity of hormonally responsive and unresponsive breast carcinoma cells. Radiat Oncol Invest 1993; 1:20.
26. Margolese R. Surgical considerations in selecting local therapy cancer: analysis at six years by the Nolvadex Adjuvant Trial Organization, Lancet 1985; 1:836.
27. Breast Cancer Trials Committee. Scottish Cancer Trials Office; Adjuvant tamoxifen in the management of operable breast cancer: the Scottish trial. Lancet 1987; 2:171.
28. Veronesi U, Luini A, Galimberti V, et al. Conservation approaches for the management of stage l/ll carcinoma of the breast: Milan Cancer Institute Trials, World J Surg 1994;18:70.
29, Vilcoq J, Calle R, Stacey p, et al. The outcome of treatment by tumorectomy and radiotherapy of patients with operable breast cancer. Int J Radiat Oncol Biol Phys 1981;7:1327.
30. Boyages J, Recht A, Connolly J, et al. Early breast cancer: predictors of breaist recurrence for patients treated with conservative surgery and radiation therapy. Radiother Oncol 1990; 19:29.
31. Kurtz J,Spitalier J, Amalric R, et al. Mammary recurrence in women younger than forty. Int J Radiat Oncol Biol Phys 1988;15:271.
32. Matthews R, McNeese M, Montague E, et al. Prognostic implications of age in breast cancer patients treated with tumorectomy and irradiation or with mastectomy. Int J Radiat Oncol Biol Phys 1988; 14:659.
33. Haffty B, Fischer D, Rose M, et al. Prognostic factors for local recurrence in the conservatively trearted breast cancer patient: a cautious interpretation of the data. J Clin Oncol 1991:9:997.
34. Rutqvist L, Pettersson D, Johansson H, Adjuvant radiation therapy versus surgery alone in operable breast cancer: long-term follow-up in a randomized clinical trial. Radiother Oncol 1993:26:104.
35. McGuire WL. Breast cancer prognostic factors: evaluation guide-lines. J Natl Cancer Inst 1990; 83:154.
36. Clark G. Prognostic and predictive factors. In: Harris J, Lippman M, Morrow M, et al. Diseases of the Breast. Philadelphia: Lippincott-Raven, 1996.
37. FoxS, Smith K, Hollyer J, et al. The epidermal growth factor receptor as a prognostic marker: results of 370 patients and review of 3009 patients. Breast Cancer Res Treat 1994; 29:41.
38. Rosen P, Lesser M, Arroyo C. p53 in node-negative breast carcinoma: an immunohistochemical study of epidemiologic risk factors, histologic features, and prognosis. J Clin Oncol 1995: 13:821.
39. Thor AD, Moore II, DH, Edgerton DM, et al, Accumulation of p53 Tumor suppressor gene protein: AnIndependent Marker of Prognosis in Breast Cancers. J Natl Cancer Inst 1992; 84:845-5.
40. Andersen J, Thorpe S, King W, et al. The prognostic value of immunohistochemical estrogen receptor analysis in paraffin-embedded and frozen sections versus that of steroid-binding assays. Eur J Cancer 1990: 26:442.
41. Muss H, Thor A, Berry D, et al. c-erbB-2 Expression and response to adjuvant therapy in women with node-positive early breast cancer. N Engl J Med 1994; 330:1260.
42. Prosser J, Thompson AM, Cranston G, et al. Evidence that p53 behaves as a tumor suppressor gene in sporadic breast tumors. Oncogene 1990; 5:1573-9.
43. Malkin D, Li FP, Strong LC, et al. Germ line p53 mutations in a familial syndrome of breast cancer. Science 1990; 250: 1233-8.
44. Trock BJ, Leonessa F,Clarke R. Multidrug resistance in breast cancer: a Meta-analysis of MR1/GP 170 Expression and its possible functional significance. J Natl Cancer Inst 1997;89:917-31.
45. Sanflippo O, Ronchi E, de Marco C, di Fronzo G, Silvestini R. Expression of P-glycoprotein in breast cancer tissue and in vitro resistance ot doxorubicin and vincristine. Eur J Cancer 1991: 27:155-8
46. Kim R. Expression of the multidrug resistance gene in human tumors. Hiroshima J Med Science 1990; 39:71-7.
47. Dixon AR, Bell F, Ellis IO, Elston CW, Blamey RW, P-glycoprotein expression in locally advanced breast cancer treated by neoadjuvant chemotherapy.BrJCancer 1992;66:537-41.
48. Prempree T, Amornmarn R, Nguyen TQ, Arce C, Failace W. Chomosome aberrations, p53 gene mutations and MDR1 amplification in Glioblastoma Multiforme. Presented at Siriraj Scientific Congress, Siriraj Hospital, Bangkok, March 1999:8-12.
49. Shapiro JR, Shapiro WR. Therapy modifies cellular heterogeneity in human malignant glioma. Acvances in Oncology 1994;8:21-9.
50. O'Shanghnessy JA, Cowan KH. Current status of Paclitaxel in the treatment of breast cancer. Breast Cancer Res Treat 1995; 33:27-37.
51. Fugua SAW. Estrogen Receptor Mutagenesis and hormone resistance. Cancer 1994; 74:1026-9.
52. Rozan S, Vincent Salomon A, Zafani B, et al. No significant predictive value of c-erbB2 or p53 expression regarding sensitivityto primarychemotherapyorradiotherapyinbreast cancer. Int J Cancer 1998; 79:27-33.
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1999-03-31
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Prempree T, Amornmarn R, Bui M, Masood S. p53 Mutation and MDR1 Overexpression in Local and Distant Failures of Breast Cancer Treated by Lumpectomy and Radiation. Thai J Surg [Internet]. 1999 Mar. 31 [cited 2024 Apr. 24];20(1):1-8. Available from: https://he02.tci-thaijo.org/index.php/ThaiJSurg/article/view/247793
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