Breast Cancer Screening Results: Section 1.b
CONTENTS:
1.7 Breast Cancer Screening Results
1.7.1 Participation Rates, Recall Rates and Cancer Detection Rates
1.7.2 The Types of Breast Abnormalities Detected (Invasive vs In-Situ Carcinoma)
1.7.3 Size of Tumors Detected in Initial Screening
1.7.4 Node-Negative Status
1.7.5 Ratio of Benign to Malignant Tumors
1.7.6 Size of Invasive Tumors
1.7.7 Ductal Carcinoma in situ (DCIS)
1.7.8 ‘Interval’ Cancers
1.8 Breast Cancer Screening Results Worldwide
1.8.1 Participation Rates in Breast Cancer Screening Programs Worldwide
1.8.2 Recall Rates Worldwide
1.8.3 Invasive Cancer Detection Rate Worldwide
1.9 Lifetime Risk of Developing Breast Cancer with Age
1.10 Inherited Genes and Genetic Testing for Breast Cancer
1.10.1 BRCA1 and BRCA2 and Genes
i. Prevalence of BRCA 1 and BRCA2 Gene Mutations
ii. Guidelines for Who Should Have Genetic Testing
iii. What To Do If You Test Positive for BRCA1 or BRCA2
1.10.2 How You Can Lower Your Chances of Having Breast Cancer, if You Have BRCA Gene Mutation?
1.10.3 Triple Negative Breast Cancer (TNBC) and Genetic Testing
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1.7 Breast Cancer Screening Results
The published literature on breast cancer screening programs worldwide provides useful statistical data. So, the information provided shows the rate of breast cancer detection, the recall rate, detection of ‘in-situ‘ and invasive breast cancer and tumor size.
From the cumulative data on breast cancer screening worldwide, it is possible to estimate the reduction in breast cancer-related mortality as a direct result of breast cancer screening.
1.7.1 Participation Rates, Recall Rates and Cancer Detection Rates
For women invited to breast cancer screening programs, the participation rate tends to be around 70%. The recall rate, for follow-up investigations, including biopsy, is typically just under 7%.
So, a majority of ‘suspicious‘ findings on breast cancer mammography turn out to be benign. Indeed, the rate of breast cancer detection is about 0.5% that is, 1 in 200 cases.
Also, in about 92% of screening mammograms patients do not require additional follow-up imaging. In addition, between 60% to 70% of women who go through a follow-up diagnostic mammogram or ultrasound and have imaging features abnormal enough to require a biopsy, will turn out to have benign breast disease only.
1.7.2 The Types of Breast Abnormalities Detected (Invasive vs In-Situ Carcinoma)
Ductal carcinoma in-situ (DCIS) is an early stage breast cancer that has not yet invaded into the breast, beyond the breast duct. When breast cancer is discovered and removed at the in-situ stage, the ‘cure’ rate is almost 100%.
However, DCIS is often detectable on a mammogram by the presence of microcalcifications. But, it is important to note that DCIS does not always present as a ‘lump’.
1.7.3 Size of Tumors Detected in Initial Screening
Microscopic analysis (pathology) of the affected breast tissue is the only way to determine the grade of breast cancer.
In the breast screening program, invasive breast cancers less than 10 mm in diameter account for 30 – 50% of tumors discovered on initial screening; larger tumors, greater than 15 mm comprise around 50% of breast cancers initially detected. A breast tumor of 15 mm is still small and treatable.
1.7.4 Node-Negative Status
‘Node-negative‘ status means that there is no metastasis of cancer cells to the lymph nodes that drain the breast.
Of breast cancers detected in initial breast screening, ‘node negative‘ status was between 70 to 75%. That is spread of breast carcinoma to the lymph nodes tends to be detected in about 25% of women screened for breast cancer.
Patients who detect breast cancer by clinical examination alone, and not by screening mammography, are about 10% more likely to have positive lymph node involvement at the time of diagnosis of breast cancer.
1.7.5 Ratio of Benign to Malignant Tumors
So, on detection of a breast tumor, a biopsy is usually necessary to assess the type of cancer and the grade of the tumor. The following data represents the ratio of benign to malignant tumors as discovered through biopsy.
It is likely that a suspicious finding sent for biopsy will turn out to be a benign breast condition unrelated to cancer.
1.7.6 Size of Invasive Tumors
The size of the tumor at initial screening is an important factor in determining the outcome for the patient and the appropriate treatment measures.
The benchmark indicator for tumor size is whether or not it is less than 10 mm in diameter, with 15 mm being a second important benchmark.
About 25% of breast cancers discovered on initial screening are less than 10 mm.
1.7.7 Ductal Carcinoma in Situ (DCIS)
Ductal carcinoma in-situ (DCIS) is a non-infiltrative cancer which is still confined to the breast duct. DCIS represents between 20% to 40% of all detected breast cancers.
The rate at which DCIS progresses to invasive cancer is around 30% of all cases over a ten year period. The prognosis for breast carcinomas discovered at the ‘in-situ‘ stage, is almost 100% positive.
1.7.8 ‘Interval’ Cancers
‘Interval’ cancers occur if you have breast cancer screening and have had a ‘clear’ mammogram and at the next screening a cancer is present.
So, ‘interval’ cancers indicate an initial ‘false negative‘ breast cancer screening results. Furthermore, this picture is typical of more aggressive forms of breast cancer.
Approximately 0.1% of women who have no breast cancer detectable on the initial screening will show breast cancer on subsequent screening. However, it is also true that a woman’s risk of developing breast cancer increases with age, so annual to bi-annual follow-up is the best screening intervals.
1.8 Breast Cancer Screening Results Worldwide
Breast cancer continues to be the commonest cancer in women worldwide, including in women in developing countries. Breast cancer incidence and breast cancer mortality rates are still increasing in most countries of Africa and Asia.
The WHO has estimated that, worldwide, more than 508,000 women died in 2011 from breast cancer. Almost 50% of cases of breast cancer and 58% of deaths from breast cancer now occur in less developed countries.
Incidence rates of breast cancer are 19.3 per 100,000 women in East Africa and 89.7 per 100,000 women in Western Europe. In developing regions of the world, the incidence rates are less than 40 per 100,000, with the lowest incidence rates in African countries. Breast cancer incidence rates are also increasing in developing countries.
Over the past 20 to 30 years, several countries are using screening programs for the early detection of breast cancer. The breast cancer screening results tend to be consistent in terms of the diagnosis of breast cancers.
Breast cancer screening results from Sweden, other European countries, the United Kingdom and Australia give similar results to those in North America for cancer detection rates.
1.8.1 Participation Rates in Breast Cancer Screening Programs Worldwide
Worldwide, the rate of participation in breast cancer screening programs tends to range between 60% and 70%. However, studies suggest that women who are more aware of health care and cancer prevention, participate more frequently in breast cancer screening.
1.8.2 Recall Rates Worldwide
If a suspicious finding is present on initial mammography, a woman may be recalled. In most cases, there are benign findings on recall.
Mammographic findings that raise a concern and cause a woman to be recalled are the presence of micro-calcifications, areas of increased breast density, and any apparent lesion with ill-defined borders and an irregular shape.
The recall rate from initial breast cancer screening tends to be between 7% and 9%; recall from additional annual screenings between 5% to 7%.
1.8.3 Invasive Cancer Detection Rate Worldwide
Worldwide, the rate for detection of invasive breast cancers on initial breast cancer screening mammogram tends to be around 0.3%.
1.9 Lifetime Risk of Developing Breast Cancer with Age
The single most significant factor influencing the risk of developing breast cancer is age. Women in their 30’s and younger have very little risk of developing breast cancer, but once a woman is over the age of 40 years, the risk begins to increase rapidly.
This is the main reason breast cancer screening is usually suggested every year to every 18 months for women aged 40 years and over. But in general terms, based on a life expectancy of 85 years, the cumulative risk for breast cancer development for all women is thought to be approximately 1 in 8.
Breast Cancer Risk according to Age
For women at the age of 30 years, the rate of breast cancer development is about 1 in 2,000. When a woman reaches 40 years of age that risk increases to about 1 in 233, and this is taken as a baseline in determining relative risk ratios from screening indicators.
As women age beyond 40 years, the risk of breast cancer development increases significantly. Women in their 50’ s have a 1 in 53 chance of breast cancer development, while a woman of age 60 years has a chance of developing breast cancer of 1 in 22.
For a 70-year-old woman, the chances of developing breast cancer are 1 in 13, and for woman 80 years and above, the chances really quite high, at 1 in 9.
So, over the entire course of a woman’s life, it is reasonable to suggest that the chances of developing breast cancer are about 1 in 8.
Table 1.1 Cumulative Lifetime Risk for Breast Cancer
Woman’s Age by decade | Cumulative Lifetime risk of breast cancer |
30 | 1 in 2000 |
40 | 1 in 233 |
50 | 1 in 53 |
60 | 1 in 22 |
70 | 1 in 13 |
80 | 1 in 9 |
Overall lifetime risk | 1 in 8 |
Table 1.2 Relative Risk for Breast Cancer
The relative risk of family history and a history of breast
abnormalities including atypical ductal hyperplasia (ADH),
breast proliferative lesions and breast papilloma which may
be detected during screening.
Risk Factor | Relative Risk for breast cancer |
Solitary Papilloma | 1.5 to 2 |
Proliferating lesions | 1.6 to 2.1 |
Personal History | 2-3 |
Family History | 2.5 |
Atypical ductal hyperplasia (ADH) | 4.4 to 5 |
ADH associated with positive family history | 8 |
Thoracic irradiation | 10 |
1.10 Inherited Genes and Genetic Testing for Breast Cancer
There are specific genetic mutations that are inherited and that predispose women to breast cancer, but these are rare. Only 5% to 6% of all breast cancer is associated with a ‘breast cancer susceptibility gene.’ These genes include:
- BRCA1
- BRCA2
- PTEN
- p53
1.10.1 BRCA1 and BRCA2 Genes
The most important of these breast cancer susceptibility genes are BRCA1 localized to chromosome 17q21, and BRCA2 localized to chromosome 13q12-13, which are mutated from their normal form. These inherited gene mutations are associated with increased susceptibility to breast and ovarian cancer in women.BRCA1 and BRCA2 mutations are inherited as autosomal dominant, highly penetrant, germline mutations
- Women with a BRCA1 mutation have a 55% to 85% increase in lifetime risk for breast cancer.
- Women with a BRCA2 mutation have a 50% to 85% increase in lifetime risk for breast cancer.
- There is an increase in ipsilateral and contralateral breast cancer in BRCA1 and BRCA2 carriers, over long follow-up periods.
- Ductal carcinoma in-situ (DCIS) occurs at an earlier age in BRCA mutation carriers than in non-carriers.
BRCA1 and BRCA2 Risk factors for Breast Cancer
BRCA1 mutation carriers may have elevated risks for cancers of the uterus, cervix, pancreas, esophagus, stomach, and prostate; the risks are not well defined.
BRCA2 mutation carriers are at increased risk of cancers of the prostate and pancreas and may have elevated risks of cancer of the stomach, gallbladder and bile duct, esophagus and skin, including melanoma.
Genetic testing is now possible in order to find out if these genes are present. Both women and men can inherit these genes, so a family history of breast cancer is an indicator for both women and men for genetic testing.
Knowledge of the presence of ‘breast cancer susceptibility genes’ may allow an individual to take steps to prevent the development of breast cancer at an early stage.
i. Prevalence of BRCA 1 and BRCA2 Gene Mutations
The prevalence of a BRCA1 or BRCA2 mutation in the general population of people of European ancestry is approximately 0.25%.
Less than 10% of all women with breast cancer, and possibly 15 per cent or more ovarian cancers, are associated with an inherited, germline (inherited) genetic mutation.
Approximately 50 % of all patients with inherited, early-onset breast cancer carry a BRCA1 or BRCA2 mutation.
ii. Guidelines for Who Should Have Genetic Testing
If there is any doubt as to whether you should have genetic testing, it is best to discuss this with a family physician first.
The current guidelines are helpful:
- If you have two or more close relatives (mother, sister, daughter) with breast or ovarian cancer, especially if one or more of the relatives were diagnosed with cancer before they turned 50 years of age.
- Or, if you have a close family member with more than one cancer, such as cancer in both breasts, or cancer in the breast and the ovary.
- Or, if you have family members from different generations (on your father or mother’s side) with breast or ovarian cancer; your grandmother, mother or sister.
- Or, if you have had a ‘triple negative’ breast cancer (TNBC), which is negative on Her-2 testing and negative for estrogen and progesterone receptors (ER and PR).
But, it is important to note the following, should you think of having genetic testing:
- Most women who have a family history of breast or ovarian cancer do not have an abnormal gene.
- If you are thinking about having genetic testing because a family member has cancer, first ask if she or he has been tested or is willing to be tested first.
- In addition, if a person with cancer does not have the mutation, it is less likely that they will have a cancer susceptibility gene.
If you decide to have genetic testing, it is advisable to talk to a genetic counsellor first. Information about contacting a genetic counsellor may be found here.
iii. What To Do If You Test Positive for BRCA1 or BRCA2:
It is important to ask your family physician and your genetic counsellor what the positive test results mean for you. This is because you will be able to find out what you can do to lower your chances of getting cancer.
You should tell members of your family about the test results as it affects their health too. Some of your family members might also want to get tested for genetic susceptibility.
1.10.2 How You Can Lower Your Chances of Having Breast Cancer if You Have BRCA Gene Mutation?
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- You can have screening for breast and ovarian cancer more often, to improve your chances of early cancer detection and early treatment.
- Surgery to remove the breasts and ovaries may be a consideration.
- You may wish to take medicines (tamoxifen) that help prevent breast cancer.
- It is possible to combine some or all of these choices.
- A monthly breast self-exam (BSE) beginning at age 18. You should learn how to perform BSE.
- A breast exam, performed by your doctor or nurse, every six months beginning at age 25.
- A mammogram once per year, beginning at age 25 (or individualized based on family history).
- A breast MRI, which is typically done alternating with a mammogram every six months, beginning at age 25 or individualized, based on family history.
1.10.3 ‘Triple Negative’ Breast Cancer (TNBC) and Genetic Testing
Triple negative breast cancers (TNBC) are those that lack Her-2, estrogen receptors (ER) and progesterone receptors (PR); these breast cancers account for approximately 15% to 20% of breast cancer diagnoses.
It is estimated that between 10% to 20% of women with TNBC have a BRCA1 mutation while a BRCA2 mutation is much less common.
Because of this association, the National Comprehensive Cancer Network (NCCN) guidelines have recommended that women with TNBC diagnosed at age 60 years or younger should be offered BRCA1/2 counselling and testing regardless of ethnicity and family history.
References:
ACCP. Recommendations on cancer screening in the European Union. Advisory Committee on Cancer Prevention. Eur J Cancer. 2000;36(12):1473. (Retrieved October 23rd, 2014): https://www.ncbi.nlm.nih.gov/pubmed/10930794
Altekruse, S.F., Kosary, C.L., Krapcho, M., et al. (2010). Surveillance, Epidemiology and End Results (SEER) Cancer Statistics Review, 1975-2007. Bethesda, Md: National Cancer Institute. (Retrieved October 23rd 2014): https://seer.cancer.gov/archive/csr/1975_2007/
Patient Information:
Breast Cancer.Org Genetics. (Retrieved February 11th 2015): https://www.breastcancer.org/risk/factors/genetics
Breast Cancer.Org Triple-Negative Breast Cancer. (Retrieved February 11th 2015): http://www.breastcancer.org/symptoms/diagnosis/trip_neg
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