Gynecology_Novak

Gynecology_Novak. In postmenopausal, estrogen receptor–positive women, chemotherapy is about one-half as effective as tamoxifen in the adjuvant setting (115). For most postmenopausal women with hormone-responsive disease (estrogen-and progesterone-responsive positivity), including node-positive patients, hormonal therapy alone may be adequate treatment. High-risk patients with hormone-resistant disease benefit from cytotoxic systemic therapy. Caution should be exercised when using chemotherapeutic agents. Patients in whom the risk of recurrence is low are likely to derive little overall benefit from the use of adjuvant systemic therapy, whereas those with a Table 40.6 Effect of Systemic Therapy on Recurrence and Survival from Breast Cancer From Early Breast Cancer Trialists’ Collaborative Group. Polychemotherapy for early breast cancer: an overview of the randomized trials. Lancet 1998;352:930, with permission.


Gynecology_Novak

Gynecology_Novak. From Early Breast Cancer Trialists’ Collaborative Group. Polychemotherapy for early breast cancer: an overview of the randomized trials. Lancet 1998;352:930, with permission. high risk of recurrence are likely to receive the greatest benefit. Comorbidities must always be considered on an individual basis. The current recommendations for adjuvant systemic therapy in breast cancer are summarized as follows: 1. Premenopausal women with lymph node involvement should be treated with adjuvant combination chemotherapy. Tamoxifen should be added for patients with estrogen receptor–positive tumors following cytotoxic therapy. 2. Premenopausal women without evidence of lymph node involvement but with large (>1 cm) size, aneuploid, or estrogen receptor–negative tumors should be treated with combination chemotherapy. Tamoxifen should be given to patients with estrogen receptor– positive tumors. 3.


Gynecology_Novak

Gynecology_Novak. 3. Postmenopausal patients with negative lymph nodes who are hormone receptor–positive should receive adjuvant aromatase inhibitor therapy as primary therapy. Those with positive lymph nodes should receive multidrug cytotoxic therapy, or a combination thereof if there are no medical contraindications. 4. Postmenopausal women with lymph node metastases who are hormone receptor– negative may be treated with adjuvant chemotherapy. 5. Adjuvant systemic therapy is not recommended for patients with favorable tumors smaller than 1 cm. Hormonal therapy may be considered if the patient’s tumor is estrogen receptor–positive. 6. Trastuzumab is recommended as adjuvant treatment in addition to chemotherapy for patients with Her-2/neu positive breast cancer, especially those with positive nodes, young women, and women with large tumors.


Gynecology_Novak

Gynecology_Novak. The treatment of advanced, metastatic breast cancer is largely palliative. For most physicians, quality-of-life issues are paramount when choosing which type of therapy is offered. In patients with locally advanced disease in conjunction with distant metastasis, palliative radiotherapy may be advised to control pain or avoid pathologic fractures. This approach is best exemplified in the treatment of isolated bone metastases, chest wall recurrences, brain metastases, and spinal cord compression.


Gynecology_Novak

Gynecology_Novak. Systemic disease may be controlled by hormonal or cytotoxic therapy. Because the quality of life during an endocrine-induced remission is usually superior to one following cytotoxic chemotherapy, it is preferable to try endocrine manipulation first. As many as one-third of patients with disseminated disease respond favorably to either functional end-organ ablation (ovary, pituitary, adrenal glands) or administration of drugs that block hormonal function. For patients with estrogen receptor–positive tumors, this response rate may be as high as 60%. Because only 5% to 10% of women with estrogen receptor–negative cancers respond to endocrine treatment, they should not routinely receive hormonal therapy except in unusual cases, such as elderly women who are intolerant of cytotoxic therapy (116).


Gynecology_Novak

Gynecology_Novak. Cytotoxic chemotherapy should be considered for the treatment of metastatic breast cancer if organ involvement is potentially life-threatening (brain, lung, or liver), if hormonal treatment is unsuccessful, if the disease has progressed after an initial response to endocrine manipulation, or if the tumor is estrogen receptor–negative. The most useful single chemotherapeutic agent is an anthracycline such as doxorubicin, which has an estimated response rate of 40% to 50%. Combination therapy using multiple agents has response rates as high as 60% to 80% (117). Clinical trials, including those investigating the use of trastuzumab for Her-2/neu-positive women with metastases, are underway to examine a variety of combinations for stage IV disease. In Her-2/neu-positive women, the trastuzumab and vinorelbine or taxane (TRAVIOTA) study showed that both regimens were active as first-line treatments for metastatic breast cancer (118). The historically prominent side effects of debilitating


Gynecology_Novak

Gynecology_Novak. and vinorelbine or taxane (TRAVIOTA) study showed that both regimens were active as first-line treatments for metastatic breast cancer (118). The historically prominent side effects of debilitating nausea and vomiting are well controlled with central-acting antiemetics. The importance of controlling these potentially devastating symptoms cannot be overemphasized.


Gynecology_Novak

Gynecology_Novak. Bisphosphonates have played an increasing role in the treatment of breast cancer that has metastasized to bone. Zoledronic acid (Zometa) was found to be superior to pamidronate (Aredia) in patients with breast cancer, with a relative risk reduction of skeletal-related events, defined as pathological fracture, spinal cord compression, radiation therapy, or surgery to bone, by an additional 16% (119). A review that compared all oral and intravenous bisphosphonates that were approved for breast cancer treatment in 2005 demonstrated a 41% risk reduction in skeletal related events with zoledronic acid versus placebo, compared with a 14% to 23% risk reduction for ibandronate (Boniva), clodronate, and pamidronate (120). Bisphosphonates may be important in preventing bone loss during hormone-based therapies for breast cancer. Bisphosphonates garnered interest as a possible adjuvant treatment for breast cancer, with early trials showing a decrease in breast cancer recurrence. Further


Gynecology_Novak

Gynecology_Novak. therapies for breast cancer. Bisphosphonates garnered interest as a possible adjuvant treatment for breast cancer, with early trials showing a decrease in breast cancer recurrence. Further investigations in randomized, controlled trials, including a trial by the Southwest Oncology Group, are comparing stages I through III breast cancer patients randomized to three different bisphosphonates prescribed after adjuvant systemic antitumor treatment.


Gynecology_Novak

Gynecology_Novak. Paget’s Disease In the 1870s, Sir James Paget described a nipple lesion similar to eczema and recognized that this nipple change was associated with an underlying breast malignancy (121). The erosion results from invasion of the nipple and surrounding areola by characteristic large cells with irregular nuclei, now called Paget cells. Although the origin of these cells is much debated by pathologists, they are probably extensions of an underlying carcinoma into the major ducts of the nipple–areolar complex. There may be no visible changes associated with the initial invasion of the nipple. Often, the patient’s presenting symptom will be nipple discharge, which is actually a combination of serum and blood from the involved ducts. The patient may have a delay in the diagnosis because the presenting symptoms are overlooked. The diagnosis is established by incisional or punch biopsy of the area of the skin changes.


Gynecology_Novak

Gynecology_Novak. The overall prognosis for patients with this rare form of breast cancer depends on the stage of the underlying malignancy. When an intraductal carcinoma alone is identified, the prognosis remains favorable, whereas patients with infiltrating ductal carcinoma metastatic to the regional lymph nodes have worse outcomes. Traditional treatment was total mastectomy and lymph node dissection, although breast conservation therapy with resection of the tumor and nipple–areolar complex, followed by whole breast radiation, is being performed in appropriately identified patients (122).


Gynecology_Novak

Gynecology_Novak. Inﬂammatory cancer, rather than infiltrating ductal carcinoma, should be diagnosed when more than one-third of the breast is involved with erythema and edema and when biopsy of the involved area, including the skin, demonstrates metastatic cancer in the subdermal lymphatics. Most of these tumors are poorly differentiated. Mammographically, the breast shows skin thickening with an infiltrative process and may or may not show a mass or calcifications. Except for biopsy of the lesion to establish the diagnosis, surgery is not part of the initial management of inﬂammatory carcinoma. Mastectomy usually fails locally within 2 years of the initial diagnosis and does not improve overall or disease-free survival rates. Better results are achieved with a combination of chemotherapy and radiation therapy. Mastectomy may be indicated for patients who remain free of distant metastatic disease after initial chemotherapy and radiation (123).


Gynecology_Novak

Gynecology_Novak. In Situ Carcinomas Both lobular and ductal carcinoma may be confined by the basement membrane of the ducts. These carcinomas do not invade the surrounding tissue and, theoretically, lack the ability to spread.


Gynecology_Novak

Gynecology_Novak. Lobular carcinoma in situ should not be considered a true malignancy but rather a risk factor for the subsequent development of invasive ductal or lobular carcinoma in either breast (124). A more appropriate nomenclature for lobular carcinoma in situ may be lobular neoplasia. Most women with lobular carcinoma in situ are premenopausal and have neither clinical nor mammographic signs of an abnormality. The lesion typically is not a discrete mass, but rather a multifocal entity within one or both breasts incidentally discovered by the pathologist during the evaluation of a completely unrelated issue. Lobular carcinoma in situ usually is managed with an excisional biopsy followed by careful surveillance with clinical breast examinations and mammography. Occasionally, a patient may request either bilateral prophylactic mastectomy or tamoxifen for chemoprevention. Women with lobular carcinoma in situ have a 1% per year and up to a 30% lifetime risk of developing an invasive cancer.


Gynecology_Novak

Gynecology_Novak. An increasingly diagnosed subtype of LCIS that has more of a pleomorphic and ﬂorid appearance appears to act in a more aggressive manner similar to ductal carcinoma in situ (DCIS). In this instance, the lesions should be managed as DCIS with wide segmental mastectomy and radiation treatment (125). DCIS is more common in postmenopausal women. It may manifest as a palpable mass but usually is detected mammographically as a cluster of branched or Y-shaped pleomorphic microcalcifications. By definition, intraductal disease does not invade beyond the basement membrane. Unlike patients with LCIS, 30% to 50% of patients with DCIS will develop an invasive ductal cancer within the same breast if treated by excisional biopsy alone (126).


Gynecology_Novak

Gynecology_Novak. Although modified radical mastectomy was previously the standard treatment for intraductal carcinoma, more conservative surgery, with or without radiation therapy, yielded good results. In NSABP trial B17, 818 patients were randomly assigned to excision alone or excision followed by radiation therapy. The mean extent of DCIS lesions was 13 mm, and 88% were larger than 20 mm. All lesions were completely resected with negative margins. After a median follow-up of 43 months, the actuarial 5-year local recurrence rate was 10.4% without radiation versus 7.5% with radiation (p = .055) for noninvasive cancers, and 10.5% without radiation versus 2.9% with radiation (p > .001) for invasive cancers. Of 83 recurrences, only 9 (11%) were not in the index quadrant. A reanalysis with a mean follow-up of 90 months confirmed these results (127). These data suggest that segmental mastectomy offers excellent local control.


Gynecology_Novak

Gynecology_Novak. Axillary metastases occur in fewer than 5% of patients diagnosed with DCIS, making routine axillary dissection unnecessary. When axillary disease is identified, further evaluation of the breast or surgical specimen or both is warranted because nodal metastases indicate that an invasive ductal component was missed. Sentinel node biopsy may be offered to certain individuals with DCIS, especially if the lesion is high grade, contains comedonecrosis, or was diagnosed on core biopsy and has clinical or radiographic features suggesting invasive disease. About 5% of patients whose initial biopsy results show intraductal carcinoma will have infiltrating ductal carcinoma when treated with mastectomy, whereas core biopsy may underestimate the invasiveness of the disease in up to 20% of patients. The incidence of contralateral breast cancer in women with intraductal carcinoma is the same as in those with invasive ductal carcinoma (5% to 8%) (128).


Gynecology_Novak

Gynecology_Novak. Breast cancer complicates 1 in 3,000 pregnancies (129,130). It is the second most common malignancy seen in association with pregnancy, surpassed only by cervical cancer. Initial studies suggested a significantly worse prognosis for patients first diagnosed during pregnancy, but data indicate that the hormonal changes associated with pregnancy seem to have little, if any, inﬂuence on prognosis. When pregnant patients are matched stage for stage with nonpregnant patients, survival rates seem equivalent (131). Patients typically present with a painless mass. Up to 60% will have concurrent lymph node involvement. The evaluation includes imaging with ultrasonography and mammography, which, although controversial, expose the fetus to less than 0.02 cGy of radiation when used with proper abdominal shielding (132). If biopsy is warranted, the procedure can be performed safely and should not be delayed until after delivery. Needle biopsy is safe and easily accomplished in the office setting.


Gynecology_Novak

Gynecology_Novak. The treatment of breast cancer in pregnant women must be highly individualized. Considerations include the patient’s age and desire to continue the pregnancy. The overall prognosis should be considered, especially when axillary lymph nodes are involved, because adjuvant chemotherapy can be teratogenic or lethal to the fetus during the first trimester, but may be given later in the pregnancy. It is believed that interruption of pregnancy does not alter the prognosis for patients with potentially curable breast cancer. Following are generalized recommendations for treatment of pregnant women with breast cancer: 1.


Gynecology_Novak

Gynecology_Novak. Traditionally, cancers diagnosed during the first or second trimester of pregnancy were treated with modified radical mastectomy. Sentinel node biopsy remains a controversial procedure in pregnancy; the use of blue dye is contraindicated as it is classified as a pregnancy category C drug, and there are serious concerns about the risk of fetal irradiation with the use of radiocolloid despite some literature supporting its safety (133). Most centers do not offer breast conservation therapy based on the theory that radiation therapy should not be given to the gravid patient. In a patient diagnosed before the third trimester, waiting until after delivery may result in an unacceptable delay in the initiation of therapy and should not be encouraged. Adjuvant chemotherapy can be given after the first trimester, although many oncologists prefer not to give it to pregnant women outside of clinical trials. A classic study reported the risk of fetal malformations to be 20% during the first


Gynecology_Novak

Gynecology_Novak. the first trimester, although many oncologists prefer not to give it to pregnant women outside of clinical trials. A classic study reported the risk of fetal malformations to be 20% during the first trimester, a rate that dropped to 1.5% during the second and third trimesters (134). Tamoxifen, however, is a class D drug and should not be given to pregnant or lactating patients with breast cancer.


Gynecology_Novak

Gynecology_Novak. 2. Localized tumors found during the third trimester of pregnancy can be managed with breast conservation therapy, with radiation delayed until after delivery, or with modified radical mastectomy. Tumors should be excised early in the third trimester using local anesthesia. If delivery is imminent, standard therapy can be performed immediately postpartum. In the patient with a viable fetus, it may be preferable to induce early labor to avoid delaying definitive cancer therapy. 3. If the breast cancer is diagnosed during lactation, lactation should be suppressed and the cancer should be treated definitively. 4. Advanced, incurable cancer should be treated with palliative therapy. Decisions regarding continuation of the pregnancy should be based on the therapy necessary and the desires of the mother.


Gynecology_Novak

Gynecology_Novak. Counseling regarding future childbearing is important for women who have had carcinoma of the breast. It was assumed that subsequent pregnancies would be detrimental because of the high levels of circulating estrogens, but there is no clear difference in survival for women who become pregnant after the diagnosis of breast cancer. One study evaluated the effect of subsequent pregnancy on overall survival after the diagnosis of early-stage breast cancer. Approximately 40% of the women in the study had node-positive disease. The 5-and 10-year survival rates were better in women who became pregnant than in matched pair controls who did not. This study suggests that subsequent pregnancy does not adversely affect the prognosis of early-stage breast cancer (135). A subsequent investigation demonstrated no increase in the relative risk of death for patients who gave birth more than 10 months after their initial diagnosis of cancer (136). Theoretically, it may be that only women with estrogen


Gynecology_Novak

Gynecology_Novak. no increase in the relative risk of death for patients who gave birth more than 10 months after their initial diagnosis of cancer (136). Theoretically, it may be that only women with estrogen receptor–positive or progesterone-positive tumors would be affected deleteriously by subsequent pregnancy, but this possibility has not been studied. Because recurrences are most frequent within the first 2 to 3 years after diagnosis, patients with receptor-positive tumors and advanced-stage disease probably should wait until after that time before becoming pregnant again.


Gynecology_Novak

Gynecology_Novak. 1. Siegel R, Ward E, Brawley O, et al. Cancer statistics, 2011. CA Cancer J Clin 2011;61:212–236. http://cacancerjournal.org 2. Anderson WF, Chu KC, Devesa SS. Distinct incidence patterns among in situ and invasive breast carcinomas, with possible etiologic implications. Breast Cancer Res Treat 2004;88:149– 159. 3. American Cancer Society. Breast cancer facts and figures 2010. Atlanta: American Cancer Society. 4. Greene MH. Genetics of breast cancer. Mayo Clin Proc 1997;72:54– 65. 5. FitzGerald MG, MacDonald DJ, Krainer M, et al. Germ-line BRCA1 mutations in Jewish and non-Jewish women with early-onset breast cancer. N Engl J Med 1996;334:143–149. 6. US Preventative Services Task Force. Genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility: recommendation statement. Ann Int Med 2005;143:355–361. 7.


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Gynecology_Novak. 6. US Preventative Services Task Force. Genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility: recommendation statement. Ann Int Med 2005;143:355–361. 7. Domchek SM, Friebel TM, Singer CF, et al. Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA 2010;304:967–975. 8. Brennan SF, Cantwell MM, Cardwell CR, et al. Dietary patterns and breast cancer risk: a systematic review and meta-analysis. Am J Clin Nutr 2010;91:1294–1302. 9. Mattisson I, Wirfalt E, Wallstrom, et al. High fat and alcohol intakes are risk factors of postmenopausal breast cancer: a prospective study from the Malmo diet and cancer cohort. Int J Cancer 2004;110:589–597. 10. Chavez-MacGregor M, Elias SG, Onland-Moret NC, et al. Post-menopausal breast cancer risk and cumulative number of menstrual cycles. Cancer Epidemiol Biomarkers Prev 2005;14:799–804. 11.


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Gynecology_Novak. 10. Chavez-MacGregor M, Elias SG, Onland-Moret NC, et al. Post-menopausal breast cancer risk and cumulative number of menstrual cycles. Cancer Epidemiol Biomarkers Prev 2005;14:799–804. 11. Eisen A, Rebbeck TR, Wood WC, et al. Prophylactic surgery in women with a hereditary predisposition to breast and ovarian cancer. J Clin Oncol 2000;18:1980–1995. 12. Russo J, Moral R, Balogh GA. The protective role of pregnancy in breast cancer. Breast Cancer Res 2005;7:131–142. 13. The Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development. Oral-contraceptive use and the risk of breast cancer. N Engl J Med 1986;315:405–411. 14. Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53,297 women with breast cancer and 100,239 women without breast cancer from 54 epidemiological studies. Lancet 1996;347:1713–1727. 15.


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Gynecology_Novak. 15. Chlebowski RT, Hendrix SL, Langer RD, et al. Inﬂuence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women’s Health Initiative Randomized Trial. JAMA 2003;289:3243–3253. 16. Gao X, Fisher SG, Enami B. Risk of second primary cancer in the contralateral breast in women treated for early-stage breast cancer: a population-based study. Int J Radiat Oncol Biol Phys 2003;56:1038– 1045. 17. Majid AS, de Paredes ES, Doherty RD, et al. Missed breast carcinoma: pitfalls and pearls. Radiographics 2003;23:881–895. 18. Bjurstam N, Bjorneld L, Duffy SW, et al. The Gothenburg Breast Cancer Screening Trial: preliminary results on breast cancer mortality for women aged 39–49. J Natl Cancer Inst Monogr 1997;22:53– 55. 19. Smith RA, Cokkinides V, Brooks D, et al. Cancer screening in the United States, 2010: a review of current American Cancer Society Guidelines and Issues in Cancer Screening. CA Cancer J Clin 2010;60:99–119. 20.


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Gynecology_Novak. 20. Bassett LW, Liu TH, Giuliano AE, et al. The prevalence of carcinoma in palpable vs nonpalpable mammographically detected lesions. Am J Roentgenol 1991;157:21–24. 21. Elmore JG, Armstrong K, Lehman CD, et al. Screening for breast cancer. JAMA 2005;293:1245–1256. 22. Collaco LM, de Lima RS, Werner B, et al. Value of fine needle aspiration in the diagnosis of breast lesions. Acta Cytol 1999;43:587– 592. 23. Morrow M. Breast. In: Greenfield LJ, Mulholland MW, Oldham KT, et al., eds. Surgery: scientific principles and practice. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2001:1334–1372. 24. Arpino G, Bardou VJ, Clark GM, et al. Infiltrating lobular carcinoma of the breast: tumor characteristics and clinical outcome. Breast Cancer Res 2004;6:R149–R156. 25. Tubiana M, Pejovic JM, Renaud A, et al. Kinetic parameters and the course of the disease in breast cancer. Cancer 1981;47:937–943. 26.


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Gynecology_Novak. 25. Tubiana M, Pejovic JM, Renaud A, et al. Kinetic parameters and the course of the disease in breast cancer. Cancer 1981;47:937–943. 26. Perrone MA, Musolino A, Michiara M, et al. Early detection of recurrences in the follow-up of primary breast cancer in an asymptomatic or symptomatic phase. Tumori 2004;90:276–279. 27. Giuliano A. The pattern of recurrence of early stage breast cancer. J Surg Oncol 1989;31:152–158. 28. Haagensen CD. Diseases of the breast. 3rd ed. Philadelphia, PA: WB Saunders, 1986. 29. American Joint Committee on Cancer. Breast. In: Edge SB, Byrd DR, Compton CC, et al., eds. AJCC cancer staging manual. 7th ed. New York: Springer, 2010:419–460. 30. Barry MC, Thornton F, Murphy M, et al. The value of metastatic screening in early primary breast cancer. Ir JMed Sci 1999;168:248– 250. 31.


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Gynecology_Novak. 30. Barry MC, Thornton F, Murphy M, et al. The value of metastatic screening in early primary breast cancer. Ir JMed Sci 1999;168:248– 250. 31. Morris PG, Lynch C, Feeney JN, et al. Integrated positron emission tomography/computed tomography may render bone scintigraphy unnecessary to investigate suspected metastatic breast cancer. J Clin Oncol 2010;28:3154–3159. 32. Halsted WS. The results of radical operation for cure of carcinoma of the breast. Ann Surg 1907;46:1–19. 33. Meyer W. Carcinoma of the breast; ten years experience with my method of radical operation. JAMA 1905;45:297–313. 34. Haagensen CD, Bodian C. A personal experience with Halsted’s radical mastectomy. Ann Surg 1984;199:143–150. 35. Dahl-Iversen E, Tobiassen T. Radical mastectomy with parasternal and supraclavicular dissection for mammary carcinoma. Ann Surg 1963;157:170–173. 36. Lewis FJ. Extended or super radical mastectomy for cancer of the breast. Minn Med 1953;36:763–766. 37.


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Gynecology_Novak. 36. Lewis FJ. Extended or super radical mastectomy for cancer of the breast. Minn Med 1953;36:763–766. 37. Urban JA. Extended radical mastectomy for breast cancer. Ann Surg 1963;106:399–404. 38. Veronesi U, Valagussa P. Inefficacy of internal mammary node dissection in breast cancer surgery. Cancer 1981;47:170–173. 39. Handley RS. The conservative radical mastectomy of Patey: 10-year results in 425 patients. Breast 1976;2:16–19. 40. Maier WP, Leber D, Rosemond GP, et al. The technique of modified radical mastectomy. Surg Gynecol Obstet 1977;145:68–74. 41. Cody HS III, Laughlin EH, Trillo C, et al. Have changing treatment patterns affected outcome of operable breast cancer? Ten year follow-up in 1288 patients, 1965 to 1978. Ann Surg 1991;213:297– 307. 42. Sacchini V, Pinotti JA, Barros AC. Nipple-sparing mastectomy for breast cancer and risk reduction: oncologic or technical problem? J Am Coll Surg 2006;203:704–714. 43.


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Gynecology_Novak. 42. Sacchini V, Pinotti JA, Barros AC. Nipple-sparing mastectomy for breast cancer and risk reduction: oncologic or technical problem? J Am Coll Surg 2006;203:704–714. 43. McWhirter R. Should more radical treatment be attempted in breast cancer? AJR Am J Roentgenol 1964;92:3–13. 44. Montague ED. Radiation therapy and breast cancer: past, present and future. Am J Clin Oncol 1985;8:455–462. 45. Montague ED, Fletcher GH. The curative value of irradiation in the treatment of nondisseminated breast cancer. Cancer 1980;46:995– 998. 46. Wallgren A, Arner O, Bergstrom J, et al. The value of preoperative radiotherapy in operable mammary carcinoma. Int J Radiat Oncol Biol Phys 1980;6:287–290. 47. Nevin JE, Baggerly JT, Laird TK. Radiotherapy as an adjuvant in the treatment of cancer of the breast. Cancer 1982;49:1194–1200. 48.


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Gynecology_Novak. 47. Nevin JE, Baggerly JT, Laird TK. Radiotherapy as an adjuvant in the treatment of cancer of the breast. Cancer 1982;49:1194–1200. 48. Fisher B, Jeong JH, Anderson S, et al. Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med 2002;347:567–575. 49. Overgaard M, Hansen P, Overgaard J, et al. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. N Engl J Med 1997;337:949–955. 50. Ragaz J, Jackson SM, Le N, et al. Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Med 1997;337:956–962. 51. Overgaard M, Jensen MB, Overgaard J, et al. Postoperative radiotherapy in high-risk postmenopausal breast cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet 1999;353:1641–1648. 52.


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Gynecology_Novak. 52. Katz A, Strom EA, Buchholz TA, et al. Locoregional recurrence patterns after mastectomy and doxorubicin-based chemotherapy: implications for postoperative irradiation. J Clin Oncol 2000;18:2817–2827. 53. Woodward WA, Strom EA, Tucker SL, et al. Locoregional recurrence after doxorubicin-based chemotherapy and postmastectomy: implications for breast cancer patients with early stage disease and predictors for recurrence after postmastectomy radiation. Int J Radiat Oncol Biol Phys 2003;57:336–344. 54. Sharma R, Bedrosian I, Lucci A, et al. Present-day locoregional control in patients with T1 or T2 breast cancer with 0 and 1 to 3 positive lymph nodes after mastectomy without radiotherapy. Ann Surg Oncol 2010;17:2899–2908. 55. Clarke M, Collins R, Darby S, et al. Effect of radiotherapy and of difference in the extent of surgery for early breast cancer on local recurrence and the 15 years survival: an overview of the randomised trials. Lancet 2005;9503:2087–2106. 56.


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Gynecology_Novak. 56. Recht A, Edge SB, Solin LJ, et al. Postmastectomy radiotherapy: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 2001;19:1539–1569. 57. Keynes G. Conservative treatment of cancer of the breast. BMJ 1937;2:643–647. 58. Calle R, Pilleron JP, Schlienger P, et al. Conservative management of operable breast cancer: ten years’ experience at the Foundation Curie. Cancer 1978;42:2045–2053. 59. Prosnitz LR, Goldenberg IS, Packard RA, et al. Radiation therapy as initial treatment for early stage cancer of the breast without mastectomy. Cancer 1977;39:917–923. 60. Harris JR, Helllman S, Silen W. Conservative management of breast cancer. Philadelphia, PA: JB Lippincott, 1983. 61. Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 2002;347:1227–1232. 62.


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Gynecology_Novak. 62. Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 2002;347:1233–1241. 63. Sarrazin D, Le MG, Arrigada R, et al. Ten-year results of a randomized trial comparing a conservative treatment to mastectomy in early breast cancer. Radiother Oncol 1989;14:177–184. 64. Jacobson JA, Danforth DN, Cowan KH, et al. Ten-year results of a comparison of conservation with mastectomy in the treatment of stage I and II breast cancer. N Engl J Med 1995;332:907–911. 65. van Dongen JA, Voogd AC, Fentiman IS, et al. Long-term results of a randomized trial comparing breast-conserving therapy with mastectomy: European Organization for Research and Treatment of Cancer 10801 trial. J Natl Cancer Inst 2000;92:1143–1150. 66.


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Gynecology_Novak. 66. Truong PT, Berthelet E, Lee J, et al. The prognostic significance of the percentage of positive/dissected axillary lymph nodes in breast cancer recurrence and survival in patients with one to three positive axillary lymph nodes. Cancer 2005;103:2006–2014. 67. National Institutes of Health. NIH consensus conference on the treatment of early-stage breast cancer. JAMA 1991;265:391–395. 68. Ivens D, Hoe AL, Podd TJ, et al. Assessment of morbidity from complete axillary dissection. Br J Cancer 1992;66:136–138. 69. Goffman TE, Laronga C, Wilson L, et al. Lymphedema of the arm and breast in irradiated breast cancer patients: risks in an era of dramatically changing axillary surgery. Breast J 2004;10:405–411. 70. Gui GP, Joubert DJ, Reichert R, et al. Continued axillary sampling is unnecessary and provides no further information to sentinel node biopsy in staging breast cancer. Eur J Surg Oncol 2005;31:707– 714. 71.


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Gynecology_Novak. 71. Changsri C, Prakash S, Sandweiss L, et al. Prediction of additional axillary metastasis of breast cancer following sentinel lymph node surgery. Breast J 2004;10:392–397. 72. Giuliano AE, Kirgan DM, Guenther JM, et al. Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg 1994;220:391–401. 73. Wilson L, Giuliano A. Sentinel lymph node mapping for primary breast cancer. Curr Oncol Rep 2005;7:12–17. 74. Krag DN, Weaver DL, Alex JC, et al. Surgical resection and radiolocalization of the sentinel lymph node in breast cancer using a gamma probe. Surg Oncol 1993;2:335–339. 75. Veronesi U, Paganelli G, Galimberti V, et al. Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes. Lancet 1997;349:1864–1867. 76.


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