BREAST CANCER NATIONAL CLINICAL PRACTICE GUIDELINES

Breast cancer remains to be one of the most common causes of death among Filipino
women. Management of this life-threatening condition continues to evolve as new
evidence on the diagnosis and treatment are discovered and/or improved.
This 2022 National Clinical Practice Guidelines (NCPG) on breast cancer aims to
provide quality evidence-based standard diagnosis and treatment guidelines for
Filipino patients with breast cancer. It aims to provide them with the best available
evidence and develop equitable and locally acceptable recommendations through
consensus building.
The multisectoral GDG convened and agreed employing the ADAPTE process to

develop these guidelines. The TAG provided the general population-intervention-
professional-outcome-healthcare setting (PIPOH) framework. The SC developed,

prioritized, and rationalized practice guideline questions based on the PIPOH. The
ERE conducted evidence-gathering, appraisal, and synthesis to answer the priority
practice guideline questions. The CP conducted eDelphi consensus-building to finalize
the recommendations on each practice guideline question. A series of online CP
meetings were held to finalize the recommendations.
14 guideline questions and 55 recommendations were developed. See summary of
recommendations below. This NCPG hopes to guide and standardize the practice in
the management of breast cancer for Filipinos.

The Department of Health (DOH) with technical assistance from East Avenue Medical
Center (EAMC) and Healthcare Practice and Policy Management, Inc. developed the
Breast Cancer (BRCA) National Clinical Practice Guideline.

The Technical Advisory Group composed of EAMC, DOH, and PhilHealth
representatives serves as the oversight committee ensuring quality and inclusive
development of the guideline.

EAMC contracted Healthcare Practice and Policy Management, Inc. (HPPM) as an
independent study group to provide highly technical assistance to develop the BRCA
NCPG through a series of consultations and evidence reviews.

The following partner organizations contributed to the success of this publication:

• East Avenue Medical Center
• Department of Health – National Integrated Cancer Control Program (DOH-
  NICCP)
• Philippine Health Insurance Corporation (PhilHealth)
• Philippine Society of Medical Oncology (PSMO)
• Philippine Radiation Oncology Society (PROS)
• Philippine College of Radiology (PCR)
• Philippine Society of General Surgeons (PSGS)
• Pain Society of the Philippines (PSP)
• Philippine Society of Breast Surgeons (PSBS)
• Philippine College of Surgeons Cancer Commission (PCS CanCom)
• Philippine Society of Hospice and Palliative Medicine (PSHPM)
• Philippine Academy of Family Physicians (PAFP)
• Philippine Society of Pathologists (PSP)
• Philippine Society for Fertility Preservation (PSFP)
• Philippine Society of Nuclear Medicine (PSNM)
• ICanServe Foundation, Inc.
• Surgical Oncology Society of the Philippines (SOSP)

Introduction

Breast cancer is a malignant proliferation of epithelial cells lining the ducts or lobules
of the breast, which primarily occurs in women older than 50 years. It can also
affect men, but it is approximately 1/150 as frequent in men as in women (Jameson et
al, 2018). According to Clemons & Goss (2001), non-modifiable risk factors like age,
sex, genetics, family history of breast cancer, history of previous breast cancer and
proliferative breast disease; and modifiable risk factors like physical activity, diet,
obesity, use of alcohol and tobacco contribute to the development of breast cancer.
Women without functioning ovaries, have early menopause, and have never received
combination estrogen/progesterone replacement therapy, are much less likely to
develop breast cancer than those who have a normal menstrual history.

Initially, the cancer is limited to a duct or lobule (in situ) with no potential for metastasis.
However, as time passes, these in situ cancers may progress and spread in the breast
tissue, lymph nodes, or other organs in the body causing the more advanced stages
of the disease. The most common symptom is a painless lump or thickening of the
breast, which may include changes in appearance, dimpling or redness in the skin,
and abnormal nipple discharge (WHO, 2020).

Breast cancer risk is increased in women with early menarche, late first full-term
pregnancy, and late menopause. These three factors account for 70-80% of the
variation in breast cancer frequency in different countries. Virtually all breast cancer
cases are diagnosed by biopsy of a nodule detected either on a mammogram or by
palpation. Only 1 in every 5-10 breast biopsies lead to a diagnosis of cancer, although
the rate of positive biopsies varies in different countries and clinical settings. Correct
staging of breast cancer patients permits accurate prognosis and is the basis of
therapeutic decision-making.

According to the Global Cancer Observatory, excluding for other cancers, breast
cancer has the highest incidence among all cancers worldwide, with approximately
2,261,419 new cases in 2020, and ranks fifth in the causes of mortality, with 684,996
deaths globally. These figures were solely based on women, resulting to breast cancer
as the leading cause of cancer deaths in females. In 2020 alone, a total of 684,996
women died of breast cancer, with a crude death rate of 17.7 per 100,000 population
(WHO International Agency for Research on Cancer, 2020).

In the Philippines, breast cancer is responsible for 10.7% of all cancer deaths and is
the third leading cause of cancer mortality in 2020, with a crude mortality rate of 18.2
per 100,000 population (GLOBOCAN, 2020).

In terms of breast cancer survival, the odds have increased dramatically over the last
35 years due to a combination of early detection and more effective therapies. After
diagnosis, survival for at least 5 years is 90% for patients in high-income countries but

much lesser for those in lower-income areas, which ranges from 40-66%. The
implementation of early detection and treatment has proven to be effective in these
high-income countries, which is being suggested to be carried out to countries with
limited resources but has the necessary standard tools (WHO, 2020).

Phase 1 – Preparation Phase

Establishment of the Guideline Development Group

The guideline development group was composed of policy makers, program
managers, medical oncologist, surgical oncologists, radiation oncologists, radiologists,
general and breast surgeons, pain and palliative specialists, primary care physicians
and family medicine doctors, fertility preservation specialist, nuclear medicine
specialists and advocacy group. The multidisciplinary and multispecialty professionals
composed the relevant working groups of the BRCA NCPG, the Technical Advisory
Group (TAG), the Steering Committee (SC), the Evidence Review Experts (ERE), and
the Consensus Panel (CP).

The TAG and the SC comprised the lead NCPG developers. The TAG has the
oversight function to ensure a quality and inclusive NCPG development process.
Nominated members for the TAG included representatives from East Avenue Medical
Center, the Department of Health, and the Philippine Health Insurance Corporation.

The multidisciplinary SC drafted the scope and target audience of the NCPG. They
also identified, ranked, and finalized the clinical questions on screening, diagnosis,
clinical management, surveillance, and pathology reporting of BRCA in the Philippines.
The SC identified, invited, reviewed, and managed the COI of the relevant working
groups, such as the steering committee, evidence reviewers, consensus panelists,
and facilitators.

The ERE provided technical assistance in evidence review ranging from the
development of the clinical questions, search and identification of evidence, appraisal
of relevant literature to answer clinical questions, and synthesis of evidence
summaries as the basis of recommendation statements. The ERE for this Guideline
included consultants with backgrounds in clinical epidemiology, information
specialists, medical informatics, and public health.

The CP was a wider group of BRCA stakeholders. Establishing a more open and
diverse group of stakeholders for the CP — including multidisciplinary healthcare
practitioners, patient advocates, DOH program managers, and other technical content
experts — was aimed at promoting transparency, introducing different perspectives to
BRCA management, and safeguarding against conflicts of interest. The CP reviewed
and revised the recommendation statements and voted on adopting these statements
into the Guideline.

Declaration and Management of Conflicts of Interest

 

The BRCA NCPG Guideline Development Group utilized the PhP 2,000,000 DOH sub-
allotment to develop the guideline. The stakeholder of the working groups that

composed the Guideline Development Group (GDG) declared no true conflict interests
related to this material. The stakeholders included in the guideline development
groups were requested to provide a summary of their conflicts of interest (COI) related
to BRCA. These COIs may be classified into financial and non-financial (or intellectual)
COI. COIs were reviewed by the ERE, and admission of a stakeholder to the GDG
was contingent on the stakeholder having no or minimal COI, following
recommendations in the DOH CPG Manual (DOH [Philippines] 2018). Conflicts of
interest(s) and how COIs were managed are presented in Annex A.

Identification of the Scope of the NCPG

The PIPOH framework was used by the TAG and the SC in defining the scope of this
Guideline, which refers to Population, Intervention, Professionals, Outcomes and
Health Care Setting (ADAPTE Collaboration, 2009). These five items aided the
selection and framing of clinical questions on Population; Intervention of interest –
screening, diagnostics, and treatment/management; Professionals to whom the
guideline will be targeted; specific Outcomes; and Health care setting and context that
the guideline will be implemented.

Generation of NCPG questions

The methodology of clinical question generation is based on frameworks of clinical
practice guidelines (CPG), agenda-setting, and consensus-building (Murphy et al,
1998; The James Lind Alliance, 2020; WHO, 2014). For CPG question development
guidelines, we specifically referred to guidance published by the WHO in 2014. Due
to the COVID-19 pandemic and mobility restrictions at the time of guideline
development, all methods of communication were virtual; no face-to-face, physical
gatherings were conducted.

PIPOH framework was used by the TAG and the SC in defining the scope of this
Guideline, which refers to Population, Intervention, Professionals, Outcomes, and
Health Care Setting (ADAPTE Collaboration, 2009).

Table 2. PIPOH Framework for the Breast Cancer NCPG Development

 

Population	Adult breast cancer stages 0-3; all types
Intervention	Diagnosis and clinical and surgical management
Professionals	Physicians/medical doctors, allied health professionals, and health policy makers
Outcomes	Overall survival rate, disease-free survival, recrrence, remission, diagnostic accuracy
Health Care Setting	Secondary and tertiary level of care

 

These recommendations were adapted from the Malaysian CPG for the Management
of Breast Cancer (3rd edition), the NCCN Guideline for Breast Cancer Version 8.2021,
2019 ESMO CPG for diagnosis, treatment, and follow-up of early breast cancer, and
Pan-Asian adapted ESMO CPG for the management of patients with early breast
cancer.

The recommendations from the Malaysian CPG were retained from its previous
version published in 2010. Similar recommendations were found in the NICE’s
guideline for early and locally advanced breast cancer and NCCN’s 2019 Breast
Cancer guideline Version 1.

The NCCN recommendations were based on a single institution retrospective chart
review of asymptomatic women with early-stage breast cancer (Stage I/II) which found
that pretreatment CBCs, LFTs, and chest x-rays did not improve detection of occult
metastatic disease but resulted in additional financial costs (Louie et al, 2015).
The Pan-Asian recommendation was adapted from the 2019 ESMO CPG for
diagnosis, treatment and follow-up of early breast cancer. The Korean experts added
HBV testing based on the 8th Korean Clinical Practice Guideline for Breast Cancer and
an article highlighting the importance of HBV screening and prevention in cancer
patients undergoing chemotherapy.

Based on NCCN, additional workup procedures include the following:

Distress Assessmen

1. Levels of distress may vary in patients and should be addressed individually.
2. We recommend assessing for distress in patients newly diagnosed with breast cancer using a validated assessment tool

Others

1. CBC, comprehensive metabolic panel, liver function, and alkaline phosphatase tests should be considered only if the patient is a candidate for preoperative or adjuvant systemic therapy. (MS-12)
2. Assess for germline BRCA1/2 mutations in all patients with recurrent or metastatic breast cancer and for patients with the following characteristics (NCCN, 2022):
   • Equal or less than 45 years of age
   • 46 to 59 years of age with ANY:
     • Unknown or limited family history
     • Multiple primary breast cancers
     • Greater than or equal to close blood relative with breast, ovarian, pancreatic, or prostate cancer at any age
   •  Greater than or equal to 51 years of age
     • Greater than or equal to one blood relative with ANY:
       1.  Breast cancer at age of less than or equal to 50 or male breast cancer at any age
       2.  Ovarian cancer at any age
       3.  Pancreatic cancer at any age
       4. Metastatic, intraductal/cribriform histology, or high- or very high-risk group prostate cancer at any ag
       5. Greater than or equal to 3 total diagnoses of breast cancer in patient and/or close blood relatives
       6. Greater than or equal to 2 close blood relatives with either breast or prostate cancer (any grade) at any age
   • Any age 
     • To aid in adjuvant decisions with Olaparib for high-risk, HER-2 negative breast cancer
     • TNBC
     •  Lobular breast cancer with personal or family history of diffuse gastric cancer
     • Male breast cancer
     • Greater than or equal to close relative with male breast cancer