Introduction
Materials and methods
Results
Sl. No. | Category | parameter | Agree | Disagree | Not Sure |
---|---|---|---|---|---|
1 | Which of the following factors are important to assess the risk of recurrence? | Age of patient | 88% | 12% | 0% |
2 | Tumor Size | 96% | 4% | 0% | |
3 | Nodal Status | 100% | 0% | 0% | |
4 | Histopathological grade of tumor | 88% | 12% | 0% | |
5 | ER expression levels | 88% | 12% | 0% | |
6 | Ki67 level | 88% | 12% | 0% | |
7 | Gene expression profiling | 88% | 0% | 12% | |
8 | On what factors is the decision for use of chemotherapy dependent? | Age of patient | 96% | 4% | 0% |
9 | Tumor Size | 88% | 12% | 0% | |
10 | Nodal Status | 100% | 0% | 0% | |
11 | Histopathological grade of tumor | 76% | 16% | 8% | |
12 | ER expression levels | 84% | 16% | 0% | |
13 | Ki67 level | 92% | 4% | 4% | |
14 | Gene expression profiling | 92% | 0% | 8% | |
15 | How useful are the online predictive tools in making decisions on chemotherapy use? | NPI | 44% | 20% | 36% |
16 | IHC4 | 56% | 20% | 24% | |
17 | PREDICT | 64% | 24% | 12% | |
18 | Choice of Multi-marker prognostic tests for deciding on prescribing chemotherapy? | Oncotype DX | 80% | 16% | 4% |
19 | CanAssist Breast | 84% | 12% | 4% | |
20 | MammaPrint | 28% | 4% | 68% | |
21 | Prosigna | 20% | 72% | 8% | |
22 | EndoPredict | 28% | 64% | 8% | |
23 | Clinical utility of multi-marker prognostic tests | Used routinely | 88% | 12% | 0% |
24 | When facing a clinical dilemma | 84% | 8% | 8% | |
25 | Based on patient affordability | 92% | 4% | 4% | |
26 | Western tests because they are part of international treatment guidelines | 92% | 8% | 0% | |
27 | Western tests are not ideal / not validated in Indian patients | 92% | 8% | 0% | |
28 | TAILORx study had few Indian/ Asian patients and hence Oncotype DX is not applicable to Asian patients | 88% | 8% | 4% | |
29 | Differences in breast cancer incidence between Asian (including Indian) versus Western women | Asian (including Indian) and Western women with EBC to be treated differently because the biology of the disease is different | 76% | 24% | 0% |
30 | Are Asian (including Indian) women diagnosed at an earlier age / during premenopausal status? | 76% | 24% | 0% | |
31 | Do Asian (including Indian) women diagnosed at an earlier age (less than 40 years) have more aggressive disease? | 84% | 16% | 0% | |
32 | Do Asian (including Indian) women below age of 45 years have high expression of proliferation genes and genes involved in endocrine resistance? | 80% | 12% | 8% | |
33 | Did the SEER Oncotype DX data show that ethnic background influences breast cancer specific mortality – specifically that black women had higher mortality compared to white women of same type, grade and stage of breast cancer? | 88% | 4% | 8% | |
34 | CanAssist Breast as a prognostic test | Does it predict risk of recurrence based on tumor biology? | 84% | 8% | 8% |
35 | Does it predict risk of recurrence across ethnic backgrounds and diverse geographies? | 76% | 12% | 12% | |
36 | Is it affordable in LMIC? | 80% | 12% | 8% | |
37 | Use of Hormonal Therapy | Does its use for more than 5 years in postmenopausal women reduce the risk of recurrence as well as the risk of contralateral breast cancer? | 92% | 4% | 4% |
38 | Is recurrence after 5 years of adjuvant endocrine therapy associated with patients identified as a high-risk group with multi-marker prognostic tests? | 80% | 20% | 0% | |
39 | Use of Hormonal Therapy in male breast cancer patients | Should it also be used for male patients? | 100% | 0% | 0% |
40 | For male patients, is the preferred choice with Tamoxifen? | 96% | 4% | 0% | |
41 | For male patients, should tamoxifen be combined with GnRHa because it further reduces estradiol levels? | 76% | 16% | 8% |
Sr No | Consensus Guidelines statements |
---|---|
1 | Patients with HR-positive HER2/neu negative early breast cancer should be treated with curative intent, unless contraindicated. |
2 | Primary tumor and regional lymph node assessment are key to optimizing therapy in this potentially curative group of EBC. |
3 | Surgery is the primary treatment for all patients with HR positive HER/neu negative EBC. In most instances, BCS is the preferred treatment that should be offered. Patients may choose to undergo BCS or MRM. |
4 | Radiation Therapy is required for all such patients undergoing BCS and selected patients undergoing MRM. |
5 | Appropriate evaluation is recommended to identify patients requiring neoadjuvant/adjuvant systemic cancer-directed therapy. |
6 | Patients suspected to have hereditary breast cancer should be evaluated with appropriate testing and counseling. |
7 | Clinical features alone are not sufficiently robust in separating patients into the low and high-risk categories. |
8 | Patient features important for predicting risk of recurrence include (in descending order of importance) nodal status; tumor size; (and of equal importance) age of patient, histopathological grade of tumor, ER expression levels, Ki67 level and gene expression profiling results. |
9 | Features important for making a decision on whether to use chemotherapy or not include (in descending order of importance) nodal status; age of the patient; Ki67 levels and gene expression profiling (of equal importance); tumor size; ER expression level; and histopathological grade of tumor. |
10 | Online predictive tools cannot be relied on and are not to be used in patient decision making. |
11 | CanAssist Breast and Oncotype DX are the recommended multi-marker prognostic tests that have substantial documented evidence. |
12 | Multi-marker prognostic tests should be used routinely if appropriate and if patients can afford them; especially when facing a clinical dilemma. |
13 | Western guidelines advocate the use of multi-marker risk assessment tools for patients with early breast cancer, based on validation predominantly in the Caucasian population. |
14 | When tests change their cutoff values and/or have different cutoff values for different age groups (like Oncotype DX), their reliability becomes questionable. This is especially important in Indian patients where a significant proportion (about 50%) are diagnosed in the premenopausal stage (early age). |
15 | Asian/Indian patients have a biologically different disease which is more aggressive in younger patients and can have higher expression of poor prognostic genes. |
16 | Regulatory authorities in India, in their breast cancer treatment guidelines, have specifically stated that such tests should not be used in clinical practice unless validated amongst Indian patients. |
17 | The only currently available predictive test for HR positive HER/neu2 negative EBC that has been validated in Indian patients is CanAssist Breast. |
18 | CanAssist Breast is also a predictive test that predicts the risk of recurrence; is applicable across ethnic backgrounds and geographies; and is affordable in LMIC. |
19 | Hormonal therapy with Tamoxifen should be used in male patients. |
20 | The use of hormonal therapy for more than 5 years reduces the risk of recurrence as well as contralateral breast cancer. |
21 | Recurrence after 5 years of endocrine therapy occurs in patients who have been identified as having high risk by multi-marker prognostic testing. |
22 | If an HR positive HER2/neu negative EBC patient demonstrates conflicting risk features (clinical low risk features with biomarker high-risk score OR clinical high-risk features. with biomarker low-risk score [Ex: CanAssist Breast score ≤ 15.5]), the biomarker risk score is more reliable. Informed discussions are recommended with patients before finalizing overall treatment plan to optimize the chance of potential cure in such patients. |
23 | The use of these practical consensus guidelines will assist real-world patient treatment decision making by avoiding the cost/ toxicity of chemotherapy in patients unlikely to benefit from it. It will also ensure that patients with a high risk of recurrence are correctly selected to receive chemotherapy as part of their potentially curative treatment plan. |
24 | These practical recommendations are applicable even during the COVID-19 pandemic since patients with HR positive HER2/neu negative early breast cancer are treated with curative intent. |
Diagnostic workup
Sl. No | Health parameter assessed | Tests required to be done |
---|---|---|
1 | General health assessment | History and menopausal status |
Physical Examination | ||
CBC (Hb, Total WBC count, % of neutrophils, platelet count) | ||
Liver function test and alkaline phosphatase as appropriate | ||
Renal Profile as appropriate | ||
Cardiac Profile as appropriate | ||
Bone mineral density test | ||
2 | Hereditary cancer assessment | When appropriate, testing for BRCA and other hereditary cancer genes (age less than 50 years, family history of breast cancer, bilateral breast cancer, etc.) |
3 | Primary tumor assessment | Mammography and/or Breast sonography |
Breast MRI only in selected cases | ||
Core Biopsy pathology (histology, ER, PR, HER2/neu, Ki67) | ||
Biomarker profiling validated in the concerned ethnic population | ||
4 | Regional lymph node assessment | Sonography of the axilla |
Sonography guided biopsy only in selected cases | ||
5 | Metastasis assessment | Additional imaging Tests for assessing the presence of distant metastasis may be done only in selected cases (if high tumor burden, aggressive biology or symptoms indicative of metastasis are present) |
Prognostic factors deciding the risk of recurrence and use of chemotherapy in HR + ve, HER/neu-ve EBC
Utility of online prognostic tools for taking decisions on chemotherapy use
Use of multi-marker prognostic test in clinical practice
Scenarios where multi-marker prognostic tests are used in clinical practice
Differences in breast cancer between Asian (including indian) versus western women
Applicability of an indian made prognostic test, CanAssist breast in making decisions on chemotherapy use
Extended hormonal therapy in high-risk HR + ve, HER2/neu-ve EBC
Use of prognostic tests for luminal sub-type
Sr No | Breast cancer subtype | Systemic therapy recommendations | Comments |
---|---|---|---|
1 | Luminal A like | Endocrine therapy alone | Chemotherapy to be added if high risk on multi-marker testing and/or high tumor burden (T3/T4 or ≥ 4 LN or G3 tumors involved) |
2 | Luminal B like, who are HER2/neu –ve | Chemotherapy followed by endocrine therapy | Chemotherapy to be avoided if low risk on multi-marker testing |