Early breast cancer can be cured in more than 90%

An overview of multimodal treatment and a tribute to resilient women

James Fleck: Anticancerweb 12 (02), 2021

Worldwide, more than 2.2 million women are diagnosed with invasive breast cancer each year. The World Health Organization (WHO) estimates an ASR = 47.8 (47.8 cases / 100,000), making breast cancer the most common malignant tumor in women. Fortunately, there is a very effective multimodal treatment. The average 5-year survival rate for non-metastatic invasive breast cancer is 91% and if the tumor is located only in the breast, without lymphatic spread, the 5-year survival rate reaches 99%. In addition, public education and technical advances in mammography were responsible for stage I diagnosis in 62% of American women. Currently, molecular diagnosis has also increased treatment specificity. Special attention has been given to triple-negative breast cancer (TNBC), which does not express receptors for estrogen, progesterone and Her-2. The 5-year survival rate tends to be lower in TNBC, making this molecular subtype a high priority for clinical trials. Fortunately, TNBC accounts for only 10-15% of breast cancer diagnosis. Most breast cancer patients (70%) have a luminal type, with a better prognosis.

Early breast cancer is defined as a localized (stage I) or regional disease (stage II), including a tumor up to 5 cm in diameter (T2) and positive lymph nodes (N1). This concept includes a wide range of breast cancer patients that can be cured using multimodal therapy. Multimodal therapy consists of surgery, radiation therapy and adjuvant or neoadjuvant systemic treatment. Whenever possible, conservative breast surgery (lumpectomy) should be recommended, as it provides equivalent survival to that of mastectomy and is cosmetically superior. Surgery also include, sentinel lymph node biopsy (SLB). Breast-conserving treatment must always be accompanied by radiation therapy. Systemic adjuvant treatment will depend on the characteristics of the tumor. Women with early stage Her2-negative, hormone-receptor (HR)-positive breast cancer should be treated with adjuvant endocrine therapy. The additional use of adjuvant chemotherapy is based on high-risk clinical characteristics ( T ≥ 2cm, N1) and evaluation of genetic phenotype provided by breast cancer multigene prognostic tests (oncotype DX and Mamma Print). TNBC (T ≥ 0.5 cm) should be treated with adjuvant chemotherapy. Her2-positive breast cancer patients (T ≥ 1 cm) should be treated with adjuvant chemotherapy and trastuzumab / pertuzumab. Following chemotherapy patients Her2-positive and HR-positive should receive endocrine therapy. The duration of treatment depends on the molecular subtype. Toxicity is manageable, since adjuvant treatment has a high therapeutic index. Whole breast radiation therapy (WBRT) should be administered to most patients undergoing conservative surgery. The timing is determined by molecular classifications and systemic adjuvant treatment recommendation. Patients treated with adjuvant chemotherapy should receive WBRT upon completion. Her2-positive early breast cancer can receive WBRT concomitant with trastuzumab / pertuzumab and HR-positive patients generally have WBRT before or concomitantly with endocrine therapy. The importance of using post-operative WBRT was well demonstrated in a metanalysis conducted by the Early Breast Cancer Triallists’ Collaborative Group revealing a significant reduction in 10-years of first recurrence risk (RR = 0.52) and 15-years risk of cancer death (RR = 0.82) when compared to conservative breast surgery alone. Currently, WBRT has been administered in a more convenient and less toxic hypofractionated schedule, using a larger fraction, but with a shorter duration. Usually, it reduces the duration of the WBRT by 2 weeks. This is also important for the public health system, since a greater number of patients can be treated with post-operative WBRT. High-risk early-breast cancer patients (N1, high-grade T2-tumor, HR-negative T2-tumor or T2-tumor expressing lymphovascular invasion) should also receive regional nodal irradiation (supra and infraclavicular LN, internal mammary nodes and axilla, in patients spared from axillary dissection). Recently, the equivalence of the two irradiation schedules (5 weeks-conventional x 3 weeks-hypofractionated) has also been demonstrated in patients with locally advanced (stage III) breast cancer treated with mastectomy. Finally, we need to recognize the effort and determination of an increasing number of more than 2 million resilient women / year, worldwide.  Fighting breast cancer, they have no face, despite being primarily responsible for each sequential therapeutic achievement shown in this breast cancer multidisciplinary approach. 

 

References:

1.     World Health Organization (WHO): Global Cancer Observatory, 2018

2.     Darby S, McGale P, Correa C, Taylor C, et al: 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. Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Lancet378(9804): 1707-16, 2011

3.     Hickey BE, James ML, Lehman M, et al: Fraction size in radiation therapy for breast conservation in early breast cancer, Cochrane Database Syst Rev., Jul 18th, 2016

4.     Shu-Lian Wang, Hui Fang, Yong-Wen Song, et al: Hypofractionated versus conventional fractionated postmastectomy radiotherapy for patients with high-risk breast cancer: a randomised, non-inferiority, open-label, phase 3 trial, Lancet Oncol, January 30th , 2019