Skip to main content Accessibility help
×
Home
  • Print publication year: 2015
  • Online publication date: November 2015

19 - Management of cancer of the breast

Summary

Introduction

Breast cancer accounts for 7% of all deaths from cancer and 15% of female deaths from cancer. It is the second most common cause of cancer death among women in the UK. Breast cancer most commonly presents as a lump in the breast, but the use of screening has also allowed very early cancers to be diagnosed before they can be detected clinically. The management of breast cancer has changed significantly over the past 50 years. Standard surgery used to be radical mastectomy and axillary node clearance, whereas today, patients are usually treated with breast-conserving techniques: wide local excision and sentinel lymph node biopsy followed by radiotherapy. The past few decades have also seen the development and wider use of systemic therapies: hormonal treatments, chemotherapy and targeted therapies such as trastuzumab. The mortality from breast cancer has steadily decreased over the last 20 years.

Anatomy

The female breast extends from the second to the sixth rib, and it is made up of 15–20 lobes which radiate out from the nipple. The nipple is surrounded by the areola. Each breast is divided into a central portion and four quadrants. The upper outer quadrant also contains the axillary tail. The lymphatic drainage from the breast is primarily to the axillary lymph nodes, but also to the internal mammary nodes, which lie in the thorax alongside the internal thoracic artery. A few lymphatic channels also communicate with those in the opposite breast and in the abdominal wall.

In the male and prepubertal female, the nipple and areola are small, and the breast tissue does not usually extend beyond the areola.

Types of tumour affecting the breast

Table 19.1 shows the range of tumours that can affect the breast. The most common are invasive ductal carcinoma and invasive lobular carcinoma. Invasive ductal carcinomas are positive for E-cadherin, whereas lobular carcinomas are negative for E-cadherin.

Incidence and epidemiology

Breast cancer is the most common malignancy in women in the UK and accounts for 30% of all new cancers in women. In 2011 there were 50,285 new cases of breast cancer in the UK, with 349 of these occurring in men.

Related content

Powered by UNSILO
Ahn, P. H., Vu, H. T., Lannin, D., et al. (2005). Sequence of radiotherapy with tamoxifen in conservatively managed breast cancer does not affect local relapse rates. J. Clin. Oncol., 23, 17–23.
Albain, K., Barlow, W., O'Malley, F., et al. (2004a). Concurrent (CAFT) versus sequential (CAF-T) chemo hormonal therapy (cyclophosphamide, doxorubicin, 5-fluorouracil, tamoxifen) versus T alone for postmenopausal, node-positive, estrogen (ER) and/or progesterone (PgR) receptor-positive breast cancer: mature outcomes and new biologic correlates on phase III intergroup trial 0100 (SWOG-8814). Breast Cancer Res. Treat., 88(Suppl. 1), A-37.
Albain, K. S., Nag, S., Calderillo-Ruiz, G., et al. (2004b). Global phase III study of gemcitabine plus paclitaxel (GT) vs. paclitaxel (T) as frontline therapy for metastatic breast cancer (MBC): first report of overall survival. Proc. Am. Soc. Clin. Oncol., 23 (5), Abstr. 510.
Anonymous, . (1996). 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, 347, 1713–1727.
Arpino, G., Bardou, V. J., Clark, G. M., et al. (2004) Infiltrating lobular carcinoma of the breast: tumor characteristics and clinical outcome. Breast Cancer Res., 6, R149–R156.
Arriagada, R., Le, M. C., Mouriesse, H., et al. (1988). Long-term effect of internal mammary chain treatment. Results of a multivariate analysis of 1195 patients with operable breast cancer and positive axillary nodes. Radiother. Oncol., 11, 213–222.
Baron, R., Ferrari, S. and Russell, R. G. 2011. Denosumab and bisphosphonates: different mechanisms of action and effects. Bone, 48, 677–692.
Barrett-Lee, P., Casbard, A., Abraham, J., et al. (2014). Oral ibandronic acid versus intravenous zoledronic acid in treatment of bone metastases from breast cancer: a randomised, open label, non-inferiority phase 3 trial. Lancet Oncol., 15, 114–122.
Bartelink, H., Horiot, J.-C., Poortmans, P., et al. (2007). Impact of a higher radiation dose on local control and survival in breast-conserving therapy of early breast cancer: 10-year results of the randomised boost versus no boost EORTC 22881-10882 trial. J. Clin. Oncol., 25, 3259–3265.
Barter, S. and Britton, P., (2014). Breast cancer. In: Recommendations for Cross-Sectional Imaging in Cancer Management, second edition. ed. Nicholson, T.. London: The Royal College of Radiologists.
Baselga, J., Campone, M., Piccart, M., et al. (2012). Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N. Engl. J. Med., 366, 520–529.
Beral, V. and Million Women Study Collaborators. (2003). Breast cancer and hormone replacement therapy in the Million Women Study. Lancet, 362, 419–427.
Bhatnagar, A. S. (2006). Review of the development of letrozole and its use in advanced breast cancer and in the neoadjuvant setting. Breast, 15 (Suppl. 1), S3–13.
Blamey, R. W. (1996). The design and clinical use of the Nottingham Prognostic Index in breast cancer. Breast, 5, 156–157.
Bliss, J. M., Kilburn, L. S., Coleman, R. E., et al. (2012). Disease-related outcomes with long-term follow-up: an updated analysis of the Intergroup Exemestane Study. J. Clin. Oncol., 30, 709–717.
Brown, J. E. and Coleman, R. E. (2002). The present and future role of bisphosphonates in the management of patients with breast cancer. Breast Cancer Res., 4, 24–29.
Citron, M. L., Berry, D. A., Cirrincione, C., et al. (2003). Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J. Clin. Oncol., 21, 1431–1439.
Cobleigh, M. A.,Vogel, C. L., Tripathy, D., et al. (1999). Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J. Clin. Oncol., 17, 2639–2648.
Cody, H. S. III. (1999). Sentinel lymph-node mapping in breast cancer. Oncology (Williston Park), 13, 25–34.
Colleoni, M., Viale, G., Zahrieh, D., et al. (2004). Chemotherapy is more effective in patients with breast cancer not expressing steroid hormone receptors: a study of preoperative treatment. Clin. Cancer Res., 10, 6622–6628.
Cooke, R., Jones, M. E., Cunningham, D., et al. (2013). Breast cancer risk following Hodgkin lymphoma radiotherapy in relation to menstrual and reproductive risk factors. Br. J. Cancer, 108, 2399–2406.
Cuzick, J., Sestak, I., Baum, M., et al. (2010). Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol., 11, 1135–1141.
Cuzick, J., Sestak, I., Pinder, S. E., et al. (2011). Effect of tamoxifen and radiotherapy in women with locally excised ductal carcinoma in situ: long-term results from the UK/ANZ DCIS trial. Lancet, 12, 21–29.
Cuzick, J., Sestak, I., Forbes, J. F., et al. (2014). Anastrozole for prevention of breast cancer in high-risk postmenopausal (IBIS-II): an international, double-blind, randomized, placebo-controlled trial. Lancet, 383: 1041–1048.
Davies, C., Pan, H., Godwin, J., et al. (2013). Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomized trial. Lancet, 381, 805–816.
De Angelis, R., Sant, M., Coleman, M. P., et al. (2014). Cancer survival in Europe 1999–2007 by country and age: results of EUROCARE-5 – a population-based study. Lancet Oncol., 15, 23–34.
Donovan, E., Bleakley, N., Denholm, E., et al. (2007). Randomised trial of standard 2D radiotherapy (RT) versus intensity modulated radiotherapy (IMRT) in patients prescribed breast radiotherapy. Radiother. Oncol., 82, 254–264.
Dubsky, P. C., Jakesz, R., Milneritsch, B., et al. (2012). Tamoxifen and anastrozole as a sequencing strategy: a randomized controlled trial in postmenopausal patients with endocrine-responsive early breast cancer from the Austrian Breast and Colorectal Cancer Study Group. J. Clin. Oncol., 30, 722–728.
Earl, H. M., Hiller, L., Dunn, J. A., et al. (2012). Adjuvant epirubicin followed by cyclophosphamide, methotrexate and fluorouracil (CMF) vs CMF in early breast cancer: results with over 7 years median follow-up from the randomized NEAT/BR9601 trials. Br. J. Cancer, 107, 1257–1267.
EBCTCG. (2005). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet, 365, 1687–1717.
EBCTCG. (2011). Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10 801 women in 17 randomised trials. Lancet, 378, 1707–1716.
EBCTCG. (2012). Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100 000 women in 123 randomised trials. Lancet, 379, 432–444.
EBCTCG. (2014). Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual data for 8135 women in 22 randomised trials. Lancet, 383, 2127–2135.
Eedarapalli, P. and Jain, S. (2006). Breast cancer in pregnancy. J. Obstet. Gynaecol., 26, 1–4.
FAST trialists group, Agrawal, R. K., Alhasso, A., et al. (2011). First results of the randomised UK FAST Trial of radiotherapy hypofractionation for treatment of early breast cancer (CRUKE/04/015). Radiother. Oncol., 100, 93–100.
Fisher, B., Montague, E., Redmond, C., et al. (1980). Findings from NSABP Protocol No. B-04-comparison of radical mastectomy with alternative treatments for primary breast cancer. I. Radiation compliance and its relation to treatment outcome. Cancer, 46, 1–13.
Fisher, B., Dignam, J., Wolmark, N., et al. (1999). Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B-24 randomised controlled trial. Lancet, 353, 1993–2000.
Fisher, B., Anderson, S., Bryant, J., et al. (2002). 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., 347, 1233–1241.
Francis, P. A., Regan, M. M., Fleming, G. F., et al. (2015). Adjuvant ovarian suppression in premenopausal breast cancer. N. Eng. J. Med., 372, 436–446.
French Adjuvant Study Group. (2001). Benefit of a high-dose epirubicin regimen in adjuvant chemotherapy for node positive breast cancer patients with poor prognostic factors: 5-year follow-up results of French Adjuvant Study Group 05 randomized trial. J. Clin. Oncol., 19, 602–611.
Geyer, C. E., Forster, J., Lindquist, D., et al. (2006). Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N. Engl. J. Med., 355, 2733–2743.
Gianni, L., Dafni, U., Gelber, R. D., et al. (2011). Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncol., 12, 236–244.
Giordano, S. H., Buzdar, A. U., Smith, T. L., et al. (2004). Is breast cancer survival improving?Cancer, 100, 44–52.
Giuliano, A. E., Hunt, K. K., Ballman, K. V., et al. (2011). Axillary dissection vs. no axillary dissection in women with invasive breast cancer and sentinel node metastasis. J. Am. Med. Assoc. 305, 569–575.
Goldhirsch, A., Gelber, R. D., Piccart-Gebhart, M. J., et al. (2013a). 2 versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomized controlled trial. Lancet. 382, 1021–1028.
Goldhirsch, A., Winer, E. P., Coates, A. S., et al. (2013b). Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann. Oncol., 24, 2206–2223.
Goodwin, A., Parker, S., Ghersi, D., et al. (2013). Post-operative radiotherapy for ductal carcinoma on situ of the breast. Cochrane Database Syst. Rev., 11. Art. No. CD000563.
Gray, R. G., Rea, D., Handley, K., et al (2013). aTTom: Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5-years in 6,953 women with early breast cancer. J. Clin. Oncol., 31(Suppl); abstr. 5.
Hanrahan, E. O., Hennessy, B. T. and Valero, V. (2005). Neoadjuvant systemic therapy for breast cancer: an overview and review of recent clinical trials. Exp. Opin. Pharmacother., 6, 1477–1491.
Harris, E. E., Christensen, V. J., Hwang, W. T., et al. (2005). Impact of concurrent versus sequential tamoxifen with radiation therapy in early-stage breast cancer patients undergoing breast conservation treatment. J. Clin. Oncol., 23, 11–16.
Haviland, J. S., Owen, J. R., Dewar, J. A., et al. (2013). The UK standardization of breast radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials. Lancet Oncol., 14, 1086–1094.
Henderson, I. C., Berry, D. A., Demetri, G. D., et al. (2003). Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J. Clin. Oncol., 21, 976–983.
Hershman, D. L., Wang, X., McBride, R., et al. (2006). Delay in initiating adjuvant radiotherapy following breast conservation surgery and its impact on survival. Int. J. Radiat. Oncol. Biol. Phys., 65, 1353–1360.
Holmberg, L., Iverson, O-E. on behalf of the HABITS Study Group. (2008). Increased risk of recurrence after hormone replacement therapy in breast cancer survivors. J. Natl Cancer Inst., 100, 475–482.
Holt, S., Bertelli, G., Humphreys, I., et al. (2013). A decision impact, decision conflict and economic assessment of routine Oncotype DX testing of 146 women with node-negative or pN1mi, ER-positive breast cancer in the UK.Br. J. Cancer, 108, 2250–2258.
Howell, A., Pippen, J., Elledge, R. M., et al. (2005). Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma: a prospectively planned combined survival analysis of two multicenter trials. Cancer, 104, 236–239.
Hughes, K. S., Schnaper, L. A., Bellon, J. R., et al. (2013). Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer: long term follow-up of CALGB 9343. J. Clin. Oncol., 31, 2382–2387.
Jin, H., Tu, D., Zhao, N., et al. (2012). Longer-term outcomes of letrozole versus placebo after 5-years of tamoxifen in the NCIC CTG MA.17 trial: analyses adjusting for treatment crossover. J. Clin. Oncol., 30, 718–721.
Joensuu, H., Bono, P., Kataja, V., et al. (2009). Fluorouracil, epirubicin and cyclophosphamide with either docetaxel or vinorelbine, with or without tastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer trial. J. Clin. Oncol., 27, 5685–5692.
Jones, A. L., Barlow, M. and Barrett-Lee, P. L. (2009a). Management of cardiac health in trastuzumab-treated patients with breast cancer: updated United kingdom National Cancer Research Institute recommendations for monitoring. Br. J. Cancer, 100, 684–692.
Jones, S., Homes, F. A., O'Shaughnessy, J., et al. (2009b). Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US Oncology Research Trial 9735. J. Clin. Oncol., 27, 1177–1183.
Karlsson, P., Cole, B. F., Colleoni, M., et al. (2011). Timing of radiotherapy and outcome in patients receiving adjuvant endocrine therapy. Int. J. Radiat. Oncol. Biol. Phys., 80, 398–402.
Kennecke, H., Yerushalmi, R., Woods, R., et al. (2010). Metastatic behavior of breast cancer subtypes. J. Clin. Oncol., 28, 3271–3277.
Kissin, M. W., Querci della Rovere, G., Easton, D., et al. (1986). Risk of lymphoedema following the treatment of breast cancer. Br. J. Surg., 73, 580–584.
Kunkler, I. H., Williams, L. W., Jack, W., et al. (2013). The PRIME II trial: wide local excision and adjuvant hormonal therapy ± postoperative whole breast irradiation in women ≥ 65-years with early breast cancer managed by breast conservation. San Antonio Breast Cancer Symposium. Abstract S2-01. Presented 11 December 2013.
Le, M. G., Arriagada, R., de Vathaire, F., et al. (1990). Can internal mammary chain treatment decrease the risk of death for patients with medial breast cancers and positive axillary lymph nodes?Cancer, 66, 2313–2318.
Leonard, R. C. and Howell, A. (2000). A systematic review of docetaxel, paclitaxel and vinorelbine in the treatment of advanced breast cancer. Adv. Breast Cancer, 2, 1–3.
Livi, L., Borghesi, S., Saivea, C., et al. (2009). Radiotherapy timing in 4,820 patients with breast cancer: University of Florence experience. Int. J. Radiat. Oncol. Biol. Phys., 73, 365–369.
Mansel, R. E., Fallowfield, L., Kissin, M., et al. (2006). Randomized multicenter trial of sentinel lymph node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC trial. J. Natl Cancer Inst., 98, 599–609.
Martin, M., Pienkowski, T., Mackey, J., et al. (2005). Adjuvant docetaxel for node-positive breast cancer. N. Engl. J. Med., 352, 2302–2313.
Marty, M., Cognetti, F., Maraninchi, D., et al. (2005). Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first line treatment: the M77001 Study Group. J. Clin. Oncol., 23, 4265–4274.
Masannat, Y. A., Bains, S. K., Pinder, S. E., et al. (2013). Challenges in the management of pleomorphic lobular carcinoma in situ of the breast. Breast, 22, 194–196.
Mauri, D., Pavlidis, N., Polyzos, N. P., et al. (2006). Survival with aromatase inhibitors and inactivators versus standard hormonal therapy in advanced breast cancer: a meta-analysis. J. Natl Cancer Inst., 98, 1285–1291.
Miller, T. W., Balko, J. M., Fox, E. M., et al. (2011). ERalpha-dependent E2F transcription can mediate resistance to estrogen deprivation in human breast cancer. Cancer Discov., 1, 338–351.
Miller, W. R., Ellis, I. O., Sainsbury, J. R. C., et al. (1994). ABC of breast diseases. Prognostic factors. Br. Med. J., 309, 1573–1576.
Morris, A. D., Morris, R. D., Wilson, J. F., et al. (1997). Breast-conserving therapy vs mastectomy in early-stage breast cancer: a meta-analysis of 10-year survival. Cancer J. Sci. Am., 3, 6–12.
Mukesh, M. B., Barnett, G. C., Wilkinson, J. S., et al. (2013). Randomized controlled trial of intensity-modulated radiotherapy for early breast cancer: 5-year results confirm superior overall cosmesis. J. Clin. Oncol., 31, 4488–4495.
NHS Cancer Screening Programmes. (2012). NHS Breast Screening Programme Annual Review.Sheffield: NHS Cancer Screening Programmes.
NICE. (2002). Guidance on the Use of Trastuzumab for the Treatment of Advanced Breast Cancer. Technology Appraisal Guidance 34. London: NICE.
NICE. (2013a). Familial Breast Cancer. NICE Clinical Guideline. http://guidance.nice.org.uk/CG164/NICEGuidance/pdf/English. London: National Institute for Health and Clinical Excellence.
NICE. (2013b). Gene Expression Profiling and Expanded Immunohistochemistry Tests for Guiding Adjuvant Chemotherapy Decisions in Early Breast Cancer Management: MammaPrint, Oncotype DX, IHC4 and Mammostrat. NICE Diagnostics Guidance 10. London: National Institute for Health and Clinical Excellence.
NICE. (2013c). Intraoperative Tests (RD-100i OSNA System and Metasin Test) for Detecting Sentinel Lymph Node Metastases in Breast Cancer. NICE Diagnostics Guidance 8. London: National Institute for Health and Clinical Excellence.
NICE. (2014). Early and Locally Advanced Breast Cancer. Diagnosis and Treatment. NICE Clinical Guideline 80.London: National Institute for Health and Care Excellence.
NIH Consensus Conference. (1991). NIH consensus conference. Treatment of early-stage breast cancer. J. Am. Med. Assoc., 265, 391–395.
Olivotto, I., Whelan, T. J., Parpia, S., et al. (2013). Interim cosmetic and toxicity results from RAPID: a randomized trial of accelerated partial breast irradiation using three-dimensional conformal external beam radiation therapy. J. Clin. Oncol., 31, 4038–4045.
O'Shaughnessy, J., Miles, D., Vukelja, S., et al. (2002). Superior survival with capecitabine plus docetaxel combination chemotherapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. J. Clin. Oncol., 20, 2812–2823.
Overgaard, M., Nielsen, H. M. and Overgaard, J. (2004). Is the benefit of post mastectomy irradiation limited to patients with 4 or more positive nodes, as recommended in international consensus reports? A subgroup analysis of the DBCG 82 b and c randomized trials.ESTRO 2004, Amsterdam, Abstr. 33.
Pagani, O., Regan, M. M., Walley, B. A., et al. (2014). Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N. Eng. J. Med., 371, 107–118.
Perou, C. M., Sørlie, T., Eisen, M. B., et al. (2000). Molecular portraits of human breast tumours. Nature, 406, 747–752.
Perez, E. A., Surman, V. J., Davidson, N. E., et al. (2011a). Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer. J. Clin. Oncol., 29, 4491–4497.
Perez, E. A., Romond, E. H., Suman, V. J., et al. (2011b). Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. J. Clin. Oncol., 29, 3366–3373.
Pignol, J-P., Olivotto, I., Rakovitch, E., et al. (2008). A multicenter randomized trial of breast intensity-modulated radiation therapy to reduce acute radiation dermatitis. J. Clin. Oncol., 26, 2085–2092.
Pinto, A. C., Azambuja, E. and Piccart-Gebhart, M. (2013). How long is enough – optimal timing of anti-HER2/neu therapy in the adjuvant setting in early breast cancer. Breast Care, 8, 264–269.
Pivot, X., Gligorov, J., Müller, V., et al. (2013a). Preference for subcutaneous or intravenous administration of trastuzumab in patients with HER2-postive early breast cancer (PrefHer): an open-label randomized study. Lancet Oncol., 14, 962–970.
Pivot, X., Romieu, G., Debled, M., et al. (2013b). 6 months versus 12 months of adjuvant trastuzumab for patients with HER2-positive early breast cancer (PHARE): a randomized phase 3 trial. Lancet Oncol., 14, 741–748.
Ragaz, J., Olivotto, I. A., Spinelli, J. J., et al. (2005). Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trialJ. Natl Cancer Inst., 97, 116–126.
Regan, M. M., Neven, P., Giobbie-Hurder, A., et al. (2011). Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up. Lancet Oncol., 12, 1101–1108.
Reid, D. M., Doughty, J., Eastell, R., et al. (2008). Guidance for the management of breast cancer treatment-induced bone loss: a consensus position statement from a UK Expert Group. Cancer Treat. Rev., 34, S1–S18.
Roché, H., Fumoleau, P., Spielmann, M., et al. (2006). Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 trial. J. Clin. Oncol., 24, 5664–5671.
Rutgers, E. J., Donker, M., Straver, M. E., et al. (2013). Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer patients: final analysis of the EORTC AMAROS trial (10981/22023). J. Clin. Oncol., 31(Suppl.); abstr LBA 1001.
Schiavon, G. and Smith, I. E. (2014). Status of adjuvant endocrine therapy for breast cancer. Breast Cancer Res., 16, 206–222.
SIGN. (2005). Management of Breast Cancer in Women. A National Clinical Guideline. No. 84. Edinburgh: Scottish Intercollegiate Guidelines Network.
SIGN. (2013). SIGN 134. Treatment of Primary Breast Cancer. A National Clinical Guideline.Edinburgh: Scottish Intercollegiate Guidelines Network.
Silverstein, M. J. (2003). The University of Southern California/Van Nuys prognostic index for ductal carcinoma in situ of the breast. Am. J. Surg., 186, 337–343.
Slamon, D. J., Leyland-Jones, B., Shak, S., et al. (2001). Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that over expresses HER2. N. Engl. J. Med., 344, 783–792.
Slamon, D., Eiermann, W., Robert, N., et al. (2011). Adjuvant trastuzumab in HER2-postive breast cancer. N. Engl. J. Med., 365, 1273–1283.
Sørlie, T., Perou, C. M., Tibshirani, R., et al. (2001). Gene expression patterns of breast carcinomas distinguish tumour subclasses with clinical implications. Proc. Natl Acad. Sci. USA, 98, 10869–10874.
Sørlie, T., Tibshirani, R., Parker, J., et al. (2003). Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc. Natl Acad. Sci. USA, 100, 8418–8423.
Sparano, J. A., Wang, M., Martino, S., et al. (2008). Weekly paclitaxel in the adjuvant treatment of breast cancer. N. Engl. J. Med., 358, 1663–1671.
Spielmann, M., Roché, H., Delozier, T., et al. (2009). Trastuzumab for patients with axillar-node-positive breast cancer: results of the FNCLCC-PACS 04 trial. J. Clin. Oncol., 27, 6129–6134.
Stopeck, A. T., Lipton, A., Body, J. J., et al. (2010). Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J. Clin. Oncol., 28, 5132–5139.
Swain, S. M., Kim, S. B., Cortes, J., et al. (2013). Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol., 14, 461–471.
Thompson, A. M., Jordan, L. B., Quinlan, P., et al. (2010). Prospective comparison of switches in biomarker status between primary and recurrent breast cancer: the Breast Recurrence In Tissues Study (BRITS). Breast Cancer Res., 12(6), R92.
Thomson, C. S., Brewster, D. H., Dewar, J. A., et al. (2004). Improvements in survival for women with breast cancer in Scotland between 1987 and 1993: impact of earlier diagnosis and changes in treatment. Eur. J. Cancer, 40, 743–753.
UICC. (2009). TNM Classification of Malignant Tumours, 7th edn, ed. Sobin, L. H., Gospodarowicz, M. and Wittekind, Ch.. New York: Wiley-Liss, pp. 181–193.
Vaidya, J. S., Wenz, F., Bulsara, M., et al. (2014). Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial. Lancet, 383, 603–613.
van de Velde, C. J. H., Rea, D., Seynaeve, C., et al. (2011). Adjuvant tamoxifen and exemstane in early breast cancer (TEAM): a ransomised phase 3 trial. Lancet, 377, 321–331.
Veronesi, U., Cascinelli, N., Mariani, L., et al. (2002). Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N. Engl. J. Med., 347, 1227–1232.
Veronesi, U., Orrechia, R., Maisonneuve, P., et al. (2013). Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomized controlled equivalence trial. Lancet Oncol., 14, 1269–1277.
Veronesi, U., Paganelli, G., Viale, G., et al. (2003). A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N. Engl. J. Med., 349, 546–553.
von Minckwitz, G., Untch, M., Blohmer, J. U., et al. (2012). Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J. Clin. Oncol., 30, 1796–1804.
Vujovic, O., Yu, E., Cherian, A., et al. (2006). Eleven-year follow-up results in the delay of breast irradiation after conservative breast surgery in node-negative breast cancer patients. Int. J. Radiat. Oncol. Biol. Phys., 64, 760–764.
Whelan, T. J., Olivotto, I., Parulekar, W. R., et al. (2015). Regional nodal irradiation in early-stage breast cancer. N. Eng. J. Med., 373, 307–316.