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9:08 AM Mon, Sept. 24th

In the Pink: History of cancer treatment

An early form of breast-conserving surgery, known as quadrantectomy (plus radiotherapy), first demonstrated survival equivalent to mastectomy in a randomized trial. Also, although chemotherapy was established for early breast cancer in the 1980s, it was first used in the late 1960s for metastatic disease. The authors explain that, in 1983, tamoxifen demonstrated, for the first time, that it can improve survival in early breast cancer. Research on the drug had begun earlier. Also, in 1993, sentinel lymph node biopsy (SNB) was shown for first time to reliably predict axillary status.

Year and Milestone

1971 The first clinical study of tamoxifen shows that it can induce temporary remission in late breast cancer

1985 A randomized trial comparing lumpectomy with mastectomy shows that disease-free and overall survival are no worse with less radical surgery

1990 The omission of radiotherapy (RT) in breast cancer patients is shown to result in high recurrence rates but has no effect on survival

1998 A meta-analysis shows that tamoxifen significantly reduces recurrence and mortality in pre- and postmenopausal women with estrogen-receptor-positive cancers, and that the longer the treatment (up to 5 years), the greater the effect

The HER2/neu oncogene is established as a prognostic factor, a predictive factor, and a target for therapy

2001 A RT boost to the tumor bed after whole-breast radiation shows significant benefit in terms of recurrence for the first time in a randomized controlled clinical trial (sponsored by the European Organization for Research and Treatment of Cancer)

2003 The first randomized clinical trial (conducted at the European Institute of Oncology) comparing SNB with axillary dissection in breast cancer shows no difference in recurrence, distant metastasis, or survival

2005 The major HERA trial shows that trastuzumab should be administered for 1 year as standard treatment for HER2-positive disease

2008 Hypofractionated RT (40 Gy given over 3 weeks) is shown to be equivalent (in recurrence rate and late toxicities) to conventional fractionation

2011 A large meta-analysis shows that RT reduces breast cancer mortality

The ACSOG Z011 trial shows that axillary dissection can be safely omitted in postmenopausal women, even if 1 or 2 sentinel nodes are positive (most patients in the trial received systemic therapy and whole-breast radiation)

2012 Ten years of adjuvant treatment with tamoxifen is shown to be significantly better than the standard 5 years in terms of reducing the risk for breast cancer recurrence and disease-specific death in the randomized controlled ATLAS trial

The first evidence that IMRT can reduce acute toxicity, compared with standard 2-dimensional RT, is published

2013 The five major subtypes of breast cancer — luminal A, luminal B, luminal B-like, HER2-positive, and triple-negative — are established

2014 An algorithm is established for the treatment of premenopausal, hormone-receptor-positive early breast cancer, and the SOFT and TEXT trials show that adjuvant treatment with the aromatase inhibitor exemestane plus ovarian suppression is associated with significantly fewer recurrences than tamoxifen plus ovarian suppression for 5 years.

The addition of pertuzumab to trastuzumab and docetaxel improves median overall survival by 15.7 months in the major CLEOPATRA clinical trial .