BREAST CANCER TIMELINE

The modern treatment of breast cancer started in the 1880s with Halsted's mastectomy but was without major innovation for roughly the next 100 years, according to an essay published in the January issue of The Breast Journal.

Then, an explosion of change began, say Stefano Zurrida, MD, and Umberto Veronesi, MD, from the European Institute of Oncology in Milan.

"The therapeutic approaches to breast cancer have changed radically since the 1990s," they write, "and the pace of change shows no signs of slacking."

A number of significant changes had their beginnings in the 1970s, including the use of chemotherapy and radiotherapy (adjuvant to surgery), they report. However, in each case, the strategies did not become more widespread until the 1980s.

Overall, the changes to treatment have been effective. The mortality rate in women with breast cancer has been declining in resource-rich countries, such as the United States, since the mid-1990s.

Still, the authors have concerns about the general state of care.

Even with fewer mastectomies, the array of therapies and follow-up monitoring now available have made breast cancer treatments "more, not less, demanding on the patient," write Drs Zurrida and Veronesi.

"They also have become massively more expensive," especially drugs and intensity-modulated radiation therapy (IMRT), the pair note, echoing many critics in the United States.

The authors review the changes in breast cancer treatment and cite seven major historic developments.

Graphic by Emily Berry

Drs Zurrida and Veronesi offer some clarifications and comments about the seven big developments. For example, it was an early form of breast-conserving surgery, known as quadrantectomy (plus radiotherapy), that 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.

Table. Other Significant Treatment Developments
Year	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