LOCALLY ADVANCED HeR 2 AND HORMONE RECEPTOR POSITIVE BREAST CANCER

Breast cancer is the malignant tumour that starts in the cells of the breast

LOCALLY ADVANCED HeR 2  AND HORMONE RECEPTOR  POSITIVE BREAST CANCER

GLOBOCON 2018 survey states that among Indian women, breast cancer is the commonest cancer overall and 1,62,468 new cases and 87,090 deaths were reported for female breast cancer in India.

Due to poor awareness of the early indicators of breast cancer, a lack of knowledge about how to perform breast self-examination, less availability of screening, the reluctancy to consult male doctors, low doctor-patient ratio, poor financial resources etc.. leads to a delay in the diagnosis of early breast cancer and the patients more often come to the doctor when the disease is symptomatic as in the case of a Locally Advanced Breast Cancer (LABC).

Locally Advanced Breast Cancer is different from the early stage and metastatic breast cancer as its treatment modality differs from the other two forms.

Recent guidelines from the U.S. National Comprehensive Cancer Network, European Society Medical Oncologist and Indian Council of Medical Research describe LABC as stage III Breast Cancer; the definition of which includes breast cancer that fulfils any of the following criteria in the absence of distant metastasis

  • Tumours more than 5 cm in size with regional lymphadenopathy (N1–3) in axilla (Fig.1).
  • Tumours of any size with direct extension to the chest wall or skin, or both including ulcer or satellite nodules), regardless of regional lymphadenopathy (Fig 2).
  • Presence of regional lymphadenopathy (clinically fixed or matted axillary lymph nodes, or any of infraclavicular, supraclavicular, or internal mammary lymphadenopathy) regardless of tumour stage.
  • Inflammatory breast cancer is another subtype of LABC that is usually separately discussed, considering its distinct clinicopathologic characteristics in contrast with non inflammatory LABC.

Investigation 

  • A complete history,
  • A core biopsy providing histology and biomarker status -Estrogen Receptor; ER, Progesterone Receptor; PR, Human Epidermal Growth factor Receptor 2; HER-2 and proliferation/grade.
  • A staging workup involving physical examination, mammography and imaging of chest and abdomen (preferably Computed Tomography scans) and bone is highly recommended. 
  • Positron Emission Tomography – Computed Tomography (PET-CT) may play a role in advanced diseases as a prognostic tool.
  • Molecular testing like the Multigene Analysis and ctDNA are not recommended in a locally advanced breast cancer.

When the investigations depict the ER, PR and HER2 status of the tumour to be positive, the tumour is called a triple positive tumour and this denotes that the tumour will respond to these targets as a modality for treatment.

Management always involves a Multidisciplinary approach involving the Medical, Surgical,Radiation Oncologists, Pathologists and Radiologists. 

Neoadjuvant chemotherapy is the best way forward in a locally advanced triple positive breast cancer.

  • Anthracycline- or taxane-based regimens would usually be considered as first-line chemotherapy.Other options are, however, available and effective, such as capecitabine and vinorelbine, particularly if avoiding alopecia is a priority for the patient.
  • Trastzumab the first approved monoclonal antibody targets the HER2 protein positive tumour cells is recommended in the first line setting along with the chemotherapy agent for HER2 positive Breast cancer.
  • Dual blockade of the HER2 positive breast Cancer with Trastuzumab and Pertuzumab in the neoadjuvant setting
  • Duration of the neoadjuvant chemotherapy is recommended for 4 – 6 cycles of chemotherapy and the approved duration for HER2 targeted therapy is 1 year (17 cycles at 52 weeks) in the adjuvant setting. However, in 2018 ASCO meeting, Helena Margaret Earl et al presented the PERSEPHONE trial that compared 6 months versus 12 months of adjuvant Trastuzumab, it was a non inferiority trial,which proved that the shorter duration is non inferior to that of the longer duration treatment with good patient compliance and significantly reduced cardiac events.

Surgery

Following the treatment modality, if the primary tumour recedes and is operable

  • surgical options like Mastectomy, lumpectomy and Breast Conserving procedures could be done.
  • while if the tumour still remains unoperable, Further continuation of systemic therapy could be considered along with radiotherapy. 

Radiotherapy is always recommended in advanced beast caners, a beam of high-energy rays are used to destroy cancer cells left behind in the breast, chest wall or lymph nodes after surgery.

When adjuvant Endocrine therapy is considered, the menopausal state of the individual plays an important role. In premenopausal women Tamoxifen is recommended and Ovarian Suppression or Ablation should be considered and discussed. In postmenopausal women Aromatase inhibitors like Anastrozole, Letrozole, Fulvestrant and Exemestane are recommended. The duration of the Endocrine Therapy for both pre and postmenopausal women is recommended for 5-10 years.

Disease progression 

Palliative care along with other treatment options as

  • Trastuzumab Emtansine (Trastuzumab linked to a potent chemotherapy agent)
  • Trastuzumab with an unused chemotherapy agent or with Endocrine Therapy,
  • Dual Bloackade using Trastuzumb&Lapatinib.
  • In the later line of treatment addition of other Chemotherapy may be considered.

Follow Up

Evaluation of response to therapy should generally occur every 2–4 months for Endocrine therapy or after two to four cycles for chemotherapy, depending on the dynamics of the disease involvement and type of treatment. Imaging of target lesions may be sufficient in many patients.In certain patients, such as those with indolent disease, less frequent monitoring is acceptable. Additional testing should be carried out in a timely manner, irrespective of the planned intervals.

Newer modalities like CDK 4/6 Inhibitors, HER2 TKIs and immunotherapy are still under investigation and clinical trial stages for the treatment of Advanced Breast Cancers.

The future research for treatment modalities in oncology should be directed towards biomarker driven Individualised Therapies and Precesion Medicines.

The advent of cost efficient biosimilars has helped the people of all strata of life to avail the otherwise costly cancer treatment worldwide. 

The number of breast cancer cases in all age groups is rising rapidly. Breast cancers in the young tend to be more aggressive than cancers in the older population, Initiatives should be taken to implement population level screening for common cancers in India which could save many precious lives and improve the quality of life of many more when diagnosed at an early stage.  

The author is Professor and Head, Medical Oncology, Saveetha University, Saveetha Medical College and Hospital, Thandalam, Chennai She is also Managing Director Addiction Healthcare

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