Thanks to an increasing amount of publicity in today’s mainstream media, the issue of female breast cancer has become a hotly discussed topic. Those affected discuss treatment or remission options, while the unaffected are eager to explore preventative measures. With information spewing from a huge array of sources however, it can be quite difficult to discern fact from fiction. Further complicating matters, opinions and medical screening guidelines often differ significantly between legal jurisdictions – differences that are not readily apparent to many of today’s net surfers.


AM I AT RISK?

Since the early 1990s, Hong Kong has experienced a noticeable rise in diagnosed cases of breast cancer, which have now become the most rampant form currently diagnosed. HKG local diagnosis rates now exist at 72 cases per 100,000 people, while the worldwide average stands at 52 cases per 100,000 people. With current statistical data, the cumulative HKG rates of both new cases and mortality are projected to continue rising. Given that these statistics are worrying, many patients seek to establish whether they are under a greater risk and naturally explore options with which to better protect themselves. The international consensus on significant risk factors and recommendations are thankfully clear, and easy to understand, being separated into primary and secondary risk factors.


BREAST CANCER RISK FACTORS


PRIMARY RISK FACTORS

The most significant primary risk factor predicting breast cancer is an established pattern of family history, thus pointing to a strong genetic correlation. Immediate family members who have been diagnosed with breast cancer after the age of 16 years is the strongest indicator, followed by more distant relatives who have been affected. Secondary to the diagnosis in relatives are the age with which they were diagnosed – with a stronger link existing if they were diagnosed at increasingly younger ages. In these criteria, first-degree relatives are defined as the immediate family, whereas second degree relatives include grandparents, aunts, uncles, nieces, nephews, half-sisters and half-brothers. Third-degree relatives would include great grandparents, great grandchildren, great aunts and uncles, first cousins, grand nephews and nieces.

The causes leading to family incidence of breast cancer are many, and include simple chance, common lifestyle and/or environmental factors, or an increase in genetic susceptibility. As of late, certain familial breast cancers have been attributed to specific mutations the cancer susceptibility genes, BRCA1 and BRCA2, which were popularized in mainstream media with Angelina Jolie’s story of total mastectomy.

The BRCA genes are responsible for cellular DNA error checking, a critical function given that cancerous tumors (cell clusters growing uncontrollably), arise when DNA errors lead to uncontrolled growth. The genes are passed from one generation to the next, but in the event that a mutated BRCA gene is present or introduced into the bloodline, it will always be expressed in the next generation – a term known as gene dominance. Because of this, the presence of a mutated BRCA1/2 gene is associated with a 40-80% lifetime risk of breast cancer, and a 15-40% lifetime risk of ovarian cancer. Some 50% of women with mutated BRCA1 genes develop breast cancer before the age of 50 years. Despite these high numbers however, it is also noteworthy to report that Western studies showed that BRCA mutation associated cancers were associated only found in 5-10% of all breast cancer cases – showing that BRCA alone was not the sole contributor. 


SECONDARY RISK FACTORS

The secondary class of breast cancer risk factors are less critical than one’s genetic history and profile, but also pose an important contributor to the development of breast cancer. They include an older age, past atypical hyperplasia or carcinoma, prior ovarian or endometrial CA, prior chest radiation therapy under 30y age, increased breast tissue density on mammogram, early menstruation (<12y), late menopause (>55y), no childbirth, late first live childbirth (>30y), obesity after menopause, HRT, no breastfeeding, alcohol consumption, and physical inactivity.



BREAST CANCER SCREENING GUIDELINES

Screening is the medical practice used to identify patients at raised probabilities of developing medical problems. With regard to breast cancer, screening methods include self-examination of one’s own breast tissue, examinations by medical clinicians, and scans (including mammography, MRI, and ultrasound). With increased information on the relevance of the BRCA gene, screening has now expanded to include the testing of its genetic presence. Recommendations between different jurisdictions however, are often conflicted, based on continually developing research information.


BRCA1/2 GENE SCREENING

Gene screening has presented itself as an extremely potent clinical tool to identify women who are at the highest levels of breast cancer risk, or whom require increased levels of cancer surveillance or even pre-emptive surgery.

Despite its clear advantage however, it is currently limited by extreme costs – in the USA, the genetic test is only available at private laboratories and fees hover in the $8,000 USD range. It is also possible that positive testing could result in repercussions such as insurance or employment policy discrimination. The HKG Workgroup thus recommends that genetic counselling first be trialed prior to proceeding with BRCA1/2 gene screening. As well, the Workgroup suggests that only those with a strong family history of breast cancer consider the screening procedure.

For women who have a clear family history of early onset breast cancer (under 45 years of age), this may be an adequate indication for BRCA1 mutation analysis as well as family screening. The council also recommended BRCA1/2 gene testing for individuals with relatives who had multiple cases of early onset breast cancer or any cancer, a family history of breast and ovarian cancer, males with breast cancer, or patients with Ashkenazi Jewish heritage.

For confirmed carriers of BRCA1/2 deleterious mutations and women with radiation to chest for treatment between age 10 and 30 years, the Working Group recommends that additional annual screening by supplementary MRI should be considered. In addition to gene screening, it is recommended that such patients consult with a cancer specialist, and hold annual breast cancer mammographies starting at age 35 or 10 years before the diagnosis of the youngest affected family member.

For women with confirmed first-degree female relatives with confirmed BRCA1/2 mutations, genetic testing should be performed for confirmation of carrier status, as well as follow-up genetic counselling and advice from medical professionals about relevant treatment or prophylactic measures.

It should be noted however, that the correlation with breast cancer and prevalence of mutated BRCA1/2 genes in ethnic Chinese populations remains uncertain, and that subsequent cancer risk estimates and management have yet to be clarified.


NON GENETIC SCREENING MEASURES

Overseas authorities have recommended that women at increased breast cancer risk (based on previously mentioned primary/secondary risk factors), begin screening at younger ages, and at more frequent intervals, although exact ages and frequency of tests have not been agreed upon. Some experts have suggested starting screening 5-10 years before the earliest incidence in a related family member, or between 25-35 in women with a confirmed BRCA1/2 mutation. Study results from the UK’s National Institute of Clinical Excellence suggested that there would be no net benefit from annual mammographic screening of BRCA mutation carriers at age 25 – 29 years; the net benefit would be zero or small at age 30 – 34 years, but there should be some benefit at age 35 or older. Other jurisdictions such as Canada have recently reached the conclusion that regular screening does not significantly increase breast cancer detection rates, and could possibly lead to false positive results – leading to increased stress and costs to both patients and local medical systems.

  Separate studies have also agreed that the rate of cancer progression is notably increased in women at increased risk of breast cancer, and thus these women should have increased surveillance frequency. The American Cancer Society recommends annual mammography for women at increased risk of breast cancer, with the addition of annual MRI for women at particularly high risk. Agencies in the UK however, recommend annual mammographic screening before age 50 then every 3 years for those aged 50 and above, for women at higher risk.



SCREENING RECOMMENDATIONS FOR THE GENERAL POPULATION

The UK and Australian health authorities believe that organized screening programs are effective methods of early tumor detection and mortality reduction, while Canadian and American authorities have recanted this previously shared framework. This change was based on the potential harm of false positive test results, where tests such as mammographies resulted in 30% over-diagnosis and over-treatment where no treatment was actually necessary.

In light of these international conflicts of opinion, the HKG health authority remains undecided on the value of routine mammography for the general HKG population.

Regardless of screening frequency, women must always remain alert for changes in the size or shape of the breast, changes in skin texture of the breast, a rash around the nipple(s), discharge from one or both nipples, new and persistent discomfort or pain in one part of the breast or armpit, and a new lump or thickening in the breast or armpit. Women should visit their doctors promptly if these symptoms appear. 


SCREENING METHODS

MAMMOGRAPHY

The mammography is a low energy x-ray scan of the localized breast area, used to detect anomalous tissue growths. The efficacy in preventing mortalities is argued widely, and its value has often been the subject of debate, but it remains the standard initial screening modality for women at increased risk of breast cancer development. It has been shown in overseas authorities that annual mammographies for those with at least two relatives with breast cancer proved to be cost-effective and a proven preventative measure. Mammographies have been shown to be sensitive in post-menopausal women, but less sensitive in women who have a genetic predisposition to breast cancer (e.g. BRCA mutations).


ULTRASOUND 

Ultrasound is often used in combination to mammographies, and can help visualize certain small breast cancers not identifiable with mammographies. It is also cheap, well tolerated and widely available.


MRI 

Emerging evidence has shown that MRI is a more sensitive method than mammography for the detection of breast cancer, and expert opinion about the potential patient benefits have led to recent overseas guidelines recommending its use for the surveillance of women at increased risk in some countries. 

Despite jurisdictional differences in MRI screening guidelines, all countries agree on annual MRIs for women at high risk with strong family history of breast cancer, or whom have confirmed BRCA gene mutations. The costs of MRIs are still prohibitively expensive however, and thus not widely used for breast cancer screening. As well, they have risks due to the need of injection contrast media, and the lack of machines and trained personnel.


GENERAL PREVENTATIVE MEASURES

Despite the availability of the finest screening techniques, a large role still exists with preventive measures. Women are advised to have regular physical activities, avoid alcohol and maintain a healthy body weight. Moreover, women are recommended to breastfeed each child for longer duration and have childbirth at an earlier age to lower their risk of breast cancer. 


References:

http://www.hkbcf.org/ (HK Breast Cancer Foundation)

HKG Center for Health Protection; 

http://www.chp.gov.hk/files/pdf/recommendations_on_breast_cancer_screening_2012.pdf


Anthony Chiam is a Pharmacist in Vancouver, Canada and regular contributor to TopDoc.