Breast cancer in Ireland: Types and treatment

BreastCheck offers women aged 50 to 69 a breast screening every two years. Out of every 1,000 women screened, on average, 993 will receive a normal result, and seven will be diagnosed with the illness, writes Donna Cosgrove PhD

In Ireland, about one in eight women are diagnosed with breast cancer (BC). Excluding non-melanoma skin cancer, BC is the most commonly diagnosed invasive cancer in women. Most women diagnosed are over 50, although it can present in younger women. The most important symptom is a breast lump, which is usually painless. Pain is, in fact, not usually a symptom.1 About one-third of BCs are diagnosed as a palpable breast mass.2 Ninety per cent of these breast lumps are benign, but they should be checked. Less common presentations include a palpable axillary mass, nipple discharge or inversion, breast asymmetry, breast skin erythema, and breast thickening.

Between 2018 and 2020, there were 3,392 cases of BC diagnosed in Ireland, with a median age of diagnosis in females of 60.3 Out of these 3,392 cases, 754 deaths were attributable to BC. For BC, five-year net survival was 88 per cent of that expected for the general population of females of the same age during 2014-2018. BC makes up 23 per cent of all cancer survivors, the greatest proportion of cancer survivors in Ireland.

The following factors increase the risk of BC:4

• Being a woman;

• Getting older;

• Family history of BC;

• Lifestyle (alcohol intake, being overweight after menopause, lack of exercise).

Types of breast cancer

The most common type of BC is invasive ductal carcinoma (50-75 per cent), followed by invasive lobular carcinoma (5 to 15 per cent) with mixed ductal/lobular carcinomas and other rarer presentations making up the rest.2 Two main targets have been identified as origins of BC. Oestrogen receptor alpha (ER?), a steroid receptor and transcription factor, is one of these, expressed in about 70 per cent of invasive BCs. When ER? is activated by oestrogen, it causes proliferation of BC cells. Expression of the progesterone receptor (PR), closely related to the ER? receptor, is also a marker of ER? signalling. Tumours expressing either ER or PR in at least 1 per cent of tumour cells are categorised as HR+. Primary systemic therapy for these ER- and PR-positive BCs includes the use of endocrine agents.

The second main molecule target is epidermal growth factor 2 (ERBB2, formerly HER2). This is a transmembrane receptor tyrosine kinase that is overexpressed in about 20 per cent of BCs, and is associated with a poor prognosis in the absence of systemic therapy.

Triple negative BC (about 15 per cent of breast tumours) lacks the expression of ER, PR or ERBB2. These tumours have a high risk of relapse in the first three to five years after diagnosis. This type of BC is more common in younger, black or hispanic women, whereas HR+ is more common in older women.

BC is staged I-IV.2 Stage I is defined as a breast tumour smaller than 2cm and no lymph node involvement; and a five-year BC specific survival of at least 99 per cent, at least 95 per cent and at least 84 per cent for HR+, ERBB2+, and triple negative subtypes respectively. Stage IV has a median overall survival of about five years for HR+ and ERBB2+ subtypes, and one year for triple negative.

Breast cancer treatment

The main goals in treatment of nonmetastatic BC are to eradicate the tumour from the breast and regional lymph nodes, and prevent metastatic occurrence. For metastatic BC, the goals are prolonging life and symptom control.

Endocrine therapy is the primary therapy for HR+/ERBB2- BC.2 This opposes oestrogen promoted tumour growth, and is given orally each day for five years. Using tamoxifen for five years reduces the recurrence of BC by about 50 per cent in this time. Tamoxifen, a selective oestrogen receptor modulator, competitively inhibits oestrogen binding to ER, and can be used in pre- and post-menopausal women. Aromatase inhibitors (eg, anastro\zole, letrozole) reduce circulating oestrogen levels through inhibition of androgen conversion to oestrogens. These are used in postmenopausal women, and are slightly more effective in reducing the recurrence of BC. Clinical trials have evaluated the benefits of taking tamoxifen and aromatase inhibitors for longer than the typical five-year duration. A small but significant improvement in BC mortality was identified, but higher rates of endometrial cancer, thromboembolic disease, osteoporosis, and fracture were observed with longer therapy. Extending endocrine therapy may in some cases be beneficial, however, it also adds toxicity. It may warrant consideration for some high-risk patients.

Chemotherapy is generally administered to all patients with triple negative breast tumours larger than 5mm. There are many neoadjuvant and adjuvant chemotherapy regimens that can be considered in early BC, and prospective clinical trials have led to established standard modern regimens. The National Cancer Control Programme has a resource page5 specifically for community pharmacies, which includes a link to a list of all national chemotherapy regimens for systemic anticancer therapy, as well as further information on cancer prevention, screening, and patient support.

The development of ERBB2-targeted therapy has been a great advancement in BC treatment. Patients with ERBB2+ tumours can benefit from targeted therapy such as anti-ERBB2 antibodies (trastuzumab and pertuzumab) and small molecule tyrosine kinase inhibitors (eg, lapatinib and neratinib).

Surgical approaches include a total mastectomy, or an excision plus radiation. Surgical management of axillary lymph nodes is considered separately. Removal is done both for diagnostic purposes (to determine the anatomic extent of the BC), and for therapeutic purposes (cancerous cell removal). Radiation therapy can be delivered to the whole breast or a portion, the chest wall, and regional lymph nodes. Radiation is usually a standard component of breast conserving therapy post lumpectomy.

BRCA (BReast CAncer) gene variants

First degree relatives of a woman diagnosed with BC have twice the risk of developing BC compared with the general population.6 BC is generally classified into either familial or sporadic cases, ie, when there is a family history, or when there is an absence of family history. The most important cause of hereditary BC is germline mutations occurring in BC susceptibility genes, eg, BRCA1, BRCA2, TP53, CHEK2, PTEN, ATM, and PPM1D. Two of the most common susceptibility genes are BRCA1 and BRCA2. Both of these BRCA proteins play a vital role in repairing breaks of double stranded DNA, which means that BRCA defective cells are highly susceptible to DNA damage and carcinogenesis.

It has been estimated that one-third of inherited BCs are due to dominant mutations of the BRCA gene. The risk of BC for carriers of BRCA1 and BRCA2 gene mutations is 10 to 20 times higher than those without mutations in these genes. A woman with a BRCA1 gene pathogenic variant has a lifetime risk (to 80 years of age) of BC of up to 90 per cent, and a lifetime risk of ovarian cancer of up to 60 per cent.7 A woman with a BRCA2 pathogenic variant has a lifetime risk of BC of up to 85 per cent and a lifetime risk of ovarian cancer of up to 30 per cent. Certain variants in these genes may also increase the risk of other cancers. Prophylactic surgery (bilateral mastectomy and/or bilateral salpingo-oophorectomy – surgery to remove fallopian tubes and ovaries) can be performed to mitigate this risk. Breast surveillance with MRI +/- mammography is recommended for women with a BRCA pathogenic variant who have not had prophylactic surgery.

A man with a BRCA2 gene pathogenic variant may have a 5 to 10 per cent lifetime risk of BC and a 25-30 per cent lifetime risk of prostate cancer. A man with BRCA1 pathogenic variant has a 0.1–1 per cent risk of BC and a prostate cancer risk, which is similar to the population risk. If an individual is identified as having a germline BRCA pathogenic variant, then it is likely that this has been inherited, and that biological relatives could also be at risk of BRCA associated cancers.

A patient with a tumour BRCA pathogenic variant is more likely to respond to PARP inhibitor therapy.

Breast screening

In Ireland, BreastCheck offers women aged 50 to 69 a breast screening every two years. Out of every 1,000 women screened for BC, on average, 993 will receive a normal result, and seven will be diagnosed with cancer. About two of the 993 women who receive a normal result will ultimately have cancer that has not been detected.4 Even with this screening women need to perform self-checks.1 The Marie Keating Foundation website8 has resources for increasing breast awareness, including a video to guide a self-check. All women known to carry a BRCA1 or BRCA2 mutation are offered annual breast screening from age 30. From age 30, women are screened with annual MRI and after 40 years of age a digital mammogram is also performed. When a woman reaches 50 years, the radiologist will decide whether your breast tissue is dense and if it is necessary to continue with MRI in addition to mammograms.9