This article talks about the different types of breast cancer present in women and treatment options available.
by Dr Tan Sing Huang
Breast cancer is the most frequent cancer among women, and the second most common cancer in the world after lung cancer. There were over 2 million new cases of breast cancer in 2018.1
However, there are certain barriers to early detection and treatment in Asian patients. These factors include a lack of knowledge and a lack of access to information about breast cancer symptoms, misconceptions about its treatments and prognosis, fear, preference for traditional or alternative medicines, cultural issues and financial concerns.2
When patients present with locally advanced tumours which have not spread to distant sites, systemic therapy in the form of chemotherapy and/or targeted therapy can be administered to shrink it so as to enable its successful removal and hopefully, the ability for the surgeon to remove the tumour without removing the entire breast (breast conservation surgery). This important decision-making process involves a multidisciplinary team including the radiologist, surgeon and medical oncologist.
Triple-Negative Breast Cancer
However, triple-negative disease is an intrinsically more aggressive breast cancer subtype and should there be recurrence, tends to involve organs such as the lung, liver and brain. As such, there have been new developments in cancer therapeutics in this area to improve the survival of these advanced breast cancer patients.
Triple-negative breast cancers are sometimes associated with BRCA mutation carriers. The presence of BRCA mutations (BRCA1 or BRCA2 mutations) can be detected from a blood test. BRCA1 and BRCA2 are genes producing proteins which suppress tumour formation, by helping to repair damaged DNA. Hence if these genes are not functioning properly due to mutations, these can cause an inability to repair DNA damage and hence give rise to a tumour. Among BRCA1 mutation carriers, at least one-third have triple-negative breast cancers.3 However, the prevalence of BRCA mutation carriers in the general population is uncommon and estimated at between 1/800 and 1/1000.4
In Jan 2018, olaparib, an oral drug became the first PARP inhibitor to be approved for metastatic breast cancer in germline BRCA mutation carriers. PARP proteins help in DNA repair and PARP inhibitors work by blocking these PARP proteins, which in an already weakened DNA repair system in BRCA mutation carriers, leads to tumour cell death. The approval was based on a phase III OlympiAD clinical trial which reported that compared to standard chemotherapy, olaparib improved the progression-free survival of advanced BRCA-related breast cancer.5
To date, immunotherapy (pembrolizumab [Keytruda], atezolizumab [Tecentriq]) has not been as widely utilised in advanced breast cancer as in other cancer types, but they have shown some promising activity in the triple-negative breast cancer subset especially when used in combination with chemotherapy, where progression-free survival has been prolonged.7 Multiple clinical trials are ongoing evaluating various immunotherapy strategies for breast cancer.
Ms K is a 48-year-old lady seeking treatment at OncoCare Cancer Centre, who presented with a large left breast mass and serous nipple discharge for a month. Mammogram showed a left breast mass measuring 40mm in the lower outer quadrant and ultrasound further confirmed this with an additional three abnormal lymph nodes seen. Breast MRI reported the mass as 70mm in longest diameter. Biopsy revealed that this tumour was an invasive ductal carcinoma grade three, estrogen and progesterone receptor negative, and HER2/neu negative. She did not have spread of disease to other areas on the PET-CT scan. She received chemotherapy with anthracycline and taxane/platinum-based drugs. The tumour responded well with marked shrinkage and surgery was able to be done with a wide local excision and sentinel lymph node biopsy.
The histology report revealed that no more tumour was present in the breast as well as lymph nodes.
Triple-negative breast cancer is a cancer which does not have any estrogen or progesterone receptors (protein receptors which attach to the hormones estrogen and progesterone which stimulates them to grow) and HER2/neu receptors (a growth-promoting protein). They account for 20 percent of all breast cancers diagnosed worldwide, with almost 200,000 cases each year.6 It is a disease which responds well to chemotherapy and if there is complete resolution of the tumour after treatment, it is a good prognostic sign for tumour recurrence. If there is no more tumour left, the cancer is less likely to recur. As such, Ms K could have a good prognosis in future.
HER2-Positive Breast Cancer
Approximately 20 percent of breast cancers overexpress human epidermal growth factor receptor 2 (HER2), a transmembrane glycoprotein epidermal growth factor receptor. Although overexpression of this receptor is associated with an overall worse prognosis, the development of HER2-targeted agents has revolutionised the management and clinical outcomes of this subtype of breast cancer.
Mdm T is a 46-year-old Indian woman who presented with a 8cm left breast tumour which was hormone-receptor positive, and HER2-positive. Unfortunately, it had also spread to involve her liver (biopsy-proven). She received anti-HER2 targeted therapy with pertuzumab and trastuzumab in addition to taxanes chemotherapy. Her breast and liver tumours resolved completely, such that she was able to undergo a left breast wide local excision as per her preference with reconstruction. She is now on maintenance anti-HER2 agents and endocrine therapy.
Trastuzumab (Herceptin) is a monoclonal antibody approved since 1998 for the treatment of metastatic HER2-positive breast cancer, but it is also used in the adjuvant post-surgery and neoadjuvant pre-surgery settings.
Pertuzumab (Perjeta) is a monoclonal antibody that binds to a different part of the HER2 receptor compared with trastuzumab. It is used in advanced, neoadjuvant and adjuvant settings in combination with chemotherapy and trastuzumab. In the advanced breast cancer setting, the combination of pertuzumab/trastuzumab/docetaxel offers about 16-month overall survival benefit over trastuzumab/docetaxel chemotherapy alone.8 In the neoadjuvant setting, adding pertuzumab to trastuzumab/docetaxel also enhances locoregional responses substantially.9
Another class of drugs with a novel formulation are antibody-drug conjugates, which are monoclonal antibodies linked to the biologically active drug, allowing its targeted delivery to diseased cells. T-DM1 is such a drug consisting of trastuzumab and the microtubule inhibitor DM-1, and it can be used in the advanced breast cancer setting.
Hormone Receptor-Positive Breast Cancer
Hormone receptor-positive tumours are often not as sensitive to chemotherapy as the latter two subtypes. However, chemotherapy often does cause tumour shrinkage, and this may be enough to allow the breast to be conserved during surgery, instead of requiring a mastectomy. However, the decision to utilise neoadjuvant chemotherapy should be one that involves a multidisciplinary team.
In advanced hormone receptor-positive disease, there are new developments in the area of endocrine therapy. The CDK4/6 pathway is overactive in breast cancer and its inhibition leads to cell cycle arrest. The CDK4/6 inhibitors (palbociclib [Ibrance], ribociclib [Kisqali], abemaciclib [Verzenio]) are a group of oral drugs that have been recently approved for use in combination with endocrine therapy for metastatic hormone-receptor positive, HER2/neu negative breast cancers.10 Many of such patients with endocrine sensitive breast cancer have benefited from these orally administered medications, which provide a higher chance of the medication working and is convenient for the patients.
Breast cancer therapeutics has made huge strides with monumental developments and ongoing clinical trials are in progress. However, challenges still exist but it is hoped that more women will survive breast cancer for much longer in the future, with a good quality of life, or hopefully avoid this disease altogether. [APBN]
References
- Globocan 2018
- Lim et al. BMJ Open 2015;5:e009863
- Peshkin et al. Breast Dis 2010; 10: 32
- Balmana et al. Annals of Oncology, Volume 20, Issue suppl_4, 1 May 2009, Pages iv19–iv20
- Robson et al. N Engl J Med. 2017;377(6):523. Epub 2017 Jun 4
- Swain S. Triple-Negative Breast Cancer: Metastatic Risk and Role of Platinum Agents 2008 ASCO Clinical Science Symposium, 2008. June 3, 2008.
- Schmid et al. N Engl J Med. 2018, 379:2108
- Swain et al. N Engl J Med. 2015;372(8):724
- Gianni et al. Lancet Oncol. 2012;13(1):25
- Pernas et al. Ther Adv Med Oncol 2018; 10: 1-15
About the Author
Dr. Tan Sing Huang is a senior consultant and medical oncologist at OncoCare Cancer Centre (Singapore).