Breast cancer

From Oncology for Medical Students

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Epidemiology

Breast cancer is the most commonly diagnosed cancer in women in Australia. By 85, one in 8 women will be diagnosed with breast cancer. It is 100 times more common in women than men with 1 in 784 men diagnosed by age 85. In 2012, more than 14600 people had a breast cancer diagnosis, and >2860 people died of breast cancer in 2010.

In each state, the incidence has increased by approximately 2% each year. The mammographic screening program BreastScreen, introduced in the 1980s, has been attributed with this increase. The greatest increase in incidence is in the women aged 50-69 years targeted by BreastScreen.

Although women from Indigenous communities, Southern Europe and Asia have lower rates of breast cancer, environmental and lifestyle factors play a role. When studying migrant communities in the higher risk areas, women acquire the risk of the host community.


Risk factors

For most sporadic breast cancer, age and female sex are the two key risk factors with most women diagnosed after menopause (median age 59). Family history especially in first or second-degree relatives is also important.

Oestrogen exposure has a role in the genesis of breast cancer, with early menarche, late menopause, and nulliparity being risk factors, and parity, history of breast feeding being protective. Although the risk of breast cancer whilst on the oral contraceptive pill is higher, the overall risk during one’s lifetime is small due to the young age at which women are on the pill. Hormone replacement therapy can increase the risk of breast cancer.

Other lifestyle related risk factors increase high caloric intake during childhood and adolescence, obesity and alcohol.

Some breast pathologies increase the risk of breast cancer such as ductal carcinoma in situ (DCIS), lobular carcinoma in situ and atypical ductal hyperplasia.


Cancer biology: Molecular and genetic basis

Breast cancer can be inherited and although up to 30% of women may have a family history, only 1-2% of the breast cancer is attributable to the BRCA1 and BRCA2 genes. Risk factors for carrying a mutation include 3 or more first or second degree relatives with breast cancer, or two relatives with significant risk factors such as male breast cancer, ovarian cancer under age 50, breast cancer under age 40, bilateral breast cancer, Ashkenazy Jewish heritage, or breast and ovarian cancer in the same patient. Other gene mutations predisposing to breast cancer include P53, PTEN, CDH1 and Peutz-Jeghers.


Clinical presentation

Approximately 55% of women present with screen-detected cancers. Other presentations include a palpable mass, skin tethering and nipple discharge. Only rarely does breast cancer present pain and erythema consistent with rare inflammatory breast cancer.


Diagnosis and staging

Although masses may be clinically suspicious, radiological diagnosis is obtained with mammogram and ultrasound and a core biopsy provides the definitive diagnosis. Although a fine needle aspiration may show a cancer, histopathology is preferred to differentiate between DCIS and invasive cancer and thus plan appropriate surgical management. Ultrasonography of the axillary lymph nodes is also standard and abnormal lymph nodes are assessed pre-operatively with a fine needle aspiration.

Pre-operative staging with CT chest, abdomen and pelvis and a bone scan are not indicated unless a neo-adjuvant approach is considered or there is a suspicion of metastatic disease.

Tumour markers such as Ca 15.3 are not sensitive for breast cancer.


Prognosis and mortality

Tumour size, higher grade, lymph node metastases, and oestrogen-receptor (ER) and progesterone-receptor (PR) negativity are poor prognostic factors in breast cancer.

However, mortality rates have decreased by about 1% each year. From 2006-2010, the 5-year breast specific survival was 89% compared to 72% from 1982-1986.


Principles of management

Breast cancer is truly multidisciplinary, involving the surgeon, medical oncologist, radiation oncologist, breast cancer nurses, psychologists, plastic surgeons, palliative care physicians, and others. Patient care is generally discussed in preoperative and postoperative multidisciplinary meetings.


Early breast cancer

Surgery for early breast cancer usually involves a wide local excision (WLE) and sentinel node biopsy (SNB). The aim is to remove the mass with a margin of normal tissue and minimise morbidity to the axilla by removing the sentinel nodes and not all the nodes. Pathologically confirmed lymphadenopathy (either preoperative or after SNB) requires an axillary dissection.

Provided adjuvant radiotherapy is given, there is no difference in overall survival between women who undergo breast conservation (WLE and adjuvant radiotherapy) versus mastectomy. Contraindications to breast conservation are previous radiotherapy, large tumour size and small breast resulting in poor cosmesis and contraindication to radiotherapy such as active SLE.

Adjuvant radiotherapy to the breast is offered to most women after breast conservation to prevent local recurrence. Women with small tumours <1 cm who are over 70 do not require adjuvant radiotherapy.

Most cancers (80%) are ER positive and therefore an anti-oestrogen agent is used for 5-10 years to decrease local recurrence, prevent systemic spread and prevent new primaries in the ipsilateral and contralateral breast. Examples include selective oestrogen receptor modulators, such as tamoxifen, and aromatase inhibitors, such as anastrozole.

Chemotherapy may be indicated in early breast cancer if a patient has poorer prognostic features such as young age, higher grade and receptor negative disease. HER-2 is a molecular marker that confers a risk towards local recurrence and systemic recurrence. As such, a HER-2 positive patient with an early breast cancer will be offered trastuzamab, a monoclonal antibody targeting the HER-2.


Locally advanced breast cancer

Some women present with locally advanced cancers that are fixed to the pectoralis muscle or involved skin, and are considered non-operable. Staging is performed in these women, and if clear, a neoadjuvant approach with pre-operative chemotherapy is undertaken in order to make the tumour ‘operable’ and control micrometastatic disease.


Metastatic disease

Breast cancer spreads initially through the lymphatics to draining lymph nodes and haematogenous spread is most commonly to bone, liver and lungs. Bone-only metastatic disease can behave less aggressively than visceral metastases. Symptomatic relief is the priority for management and may include an anti-oestrogen tablet such as tamoxifen if hormone receptor positive, radiotherapy for bony pain or to prevent fractures, and sometimes even surgery for local control.


Follow-up and survivorship

Most breast cancer patients are followed-up indefinitely by the multidisciplinary team. Annual mammography is advised and a 3-6 months interval for follow-up is advised for the first 2 years.

Many survivorship and supportive care plans are organised by breast care nurses to ensure good preventative measures are taken and to address the impact of breast cancer on quality of life issues such as mood, body image and sexuality.


Screening and prevention

BreastScreen Australia is a funded program for asymptomatic women aged 50-69 to undergo two yearly mammograms. Approximately 60% of the eligible female population attend. Early detection is the aim, with a two-fold increase in the number of small tumours <1 cm detected during the first and second decade of mammographic screening. Approximately 20% of the tumours diagnosed are DCIS.

Since 2009, women under 50 who are considered at high risk of breast cancer (>30% lifetime risk due to family) are able to have screening with MRI in addition to mammography. Smaller tumours are more difficult to detect in dense breasts. These women are also offered tamoxifen as a preventative medication, which decreases the chance of breast cancer at 10 years, by 40%. Prophylactic surgery by way of mastectomy confers a 95-97% risk reduction in gene mutation carriers.


Case study 1

Laura is a 62 year old who presented to BreastScreen for a routine mammogram. She has a new mass seen and has an ultrasound guided core biopsy which confirms a 1.8 cm invasive ductal breast cancer. No abnormal lymph nodes are detected on US.

She is referred to a surgeon who offers her a wide local excision and sentinel node biopsy as a day case. Her pathology reveals a 21 mm invasive ductal carcinoma which is ER+ve, PR+ve and HER-2 negative. Two sentinel nodes are removed and do no have metastatic disease.

She is then referred to the radiation oncologist who recommends 5 weeks of radiotherapy (50 Gray) and sees the medical oncologist who recommends tamoxifen.

At three years post diagnosis, she continues with tamoxifen and tolerates the hot flushes which result from her tablet. She has been having annual mammography and she continues to work and play tennis regularly.


Case study 2

Belinda is a 35 year old whose grandmother had ovarian cancer and mother died of breast cancer at age 34. Her two other aunts were diagnosed with breast cancer in their early 40s. One aunt is found to be a BRCA1 carrier. Belinda undergoes genetic testing and is also found to be a BRCA1 carrier.

She undergoes her first surveillance with mammogram and MRI which are normal. She presents 8 months later prior to her next surveillance with a 1.2 cm mass in the right medial breast. This is confirmed to be a triple negative (ER-, PR-, HER2 -) cancer. She chooses to have a bilateral mastectomy, implant reconstruction and sentinel node biopsy on the right side.

She is node negative and the tumour size is 12 mm. As she is a BRCA1 carrier, she has chemotherapy. During the last cycle of chemotherapy she complains of back pain. Staging is performed and she has widespread bony metastases. She receives some radiotherapy to her right hip to prevent fractures and is commenced on oral morphine.

She decreases her work to three days a week, but she is found drowsy in bed three months later. She is admitted to hospital and a CT reveals widespread brain metastases and pulmonary and liver metastases. She receives whole brain irradiation and is admitted to the palliative care unit. She dies three weeks later, 14 months after her diagnosis.

Key points

Breast cancer has an excellent survival in early disease in older women. Young age and mutations such as BRCA1 can result in a more aggressive course.

References

  1. Australian Institute of Health and Welfare. Cancer. [homepage on the internet] Australia: AIHW; 2013 [cited 2014 May 29; updated 2013]. Available from: http://www.aihw.gov.au/cancer/
  2. National Breast Cancer Centre. Clinical practice guidelines management of early breast cancer: Second edition. Canberra: National Health and Medical Research Clinic; 2001 Aug [cited 2014 May 29] Available from: http://www.nhmrc.gov.au/_files_nhmrc/publications/attachments/cp74_management_early_breast_cancer_131223.pdf
  3. Cancer Council Australia. Cancer Council Australia. [homepage on the internet] Australia: Cancer Council Australia; 2014 Jan 1 [cited 2014 May 29; updated 2014 Jan 1]. Available from: http://www.cancer.org.au/
  4. Cancer Epidemiology Centre. CanStat digests. [homepage on the internet] Victoria: Cancer Council Victoria; 2014 [cited 2014 May 29; updated 2014]. Available from: http://www.cancervic.org.au/research/registry-statistics/canstats