Several clinical studies in women have suggested that chasteberry (Vitex agnus castus) is efficacious in reducing symptoms associated with premenstrual symptoms (PMS) including mastalgia.^2,³ This herb contains steroidal precursors and active moieties including progesterone, testosterone and androstenedione. Chasteberry may interact with oral contraceptives, other hormonal therapy and dopazmine antagonists such as haloperidol and prochlorperazine. Adverse effects reported include nausea, rash, headache and agitation.

If symptoms remain unresponsive to these therapies, consider referral. A range of medications are available to specialist practitioners, including bromocryptine, danazol, tamoxifen and goserelin.

Benign breast lumps

Fibroadenomata

Fibroadenomata result from a focal proliferation of benign breast elements, both epithelial and stromal, and are influenced by hormonal factors. They may fluctuate during the menstrual cycle and pregnancy. They are most common in the 20–30 year age group and are uncommon post menopause.

On clinical examination they are typically smooth, mobile, rubbery masses, which may be tender, especially premenstrually. They may be single or multiple. On breast ultrasound they appear as a well-defined ovoid homogenously hypoechoic mass with smooth margins and increased through transmission.

Diagnosis is confirmed by non-excisional biopsy. Ultrasound-guided core biopsy is used more commonly because of the high proportion of fibrous tissue to epithelial tissue, which increases the risk of not sampling the epithelial cells on fine needle aspiration.

Once the diagnosis is confirmed, fibroadenomata may be managed by either surgical excision or regular clinical and imaging review over 12–18 months until the lesion is proved to be stable. Should the lesion significantly increase in size or develop atypical features on imaging, it should undergo excision biopsy. New palpable fibroadenomas in women aged over 40 years should be referred to a breast surgeon for consideration of excision biopsy, because the likelihood of a new lump being cancer increases with age.⁴

Phyllodes tumour is a rare fibroepithelial tumour that produces a spectrum of diseases ranging from benign (with a significant risk of local recurrence) to malignant (sometimes with rapidly growing metastases). Clinically they may be indistinguishable from fibroadenoma, presenting as a smooth, rounded, painless breast lump that has continued to increase in size. Their appearance on mammogram and ultrasound may also resemble fibroadenomata. Diagnosis is confirmed by histology following excision biopsy.

FIGURE 51.2 Fibroadenoma: A Mammogram showing two well-defined masses; B Ultrasound of the lesion nearer the nipple in A

Breast cysts

Breast cysts are distended and involuted lobules. They are hormonally responsive and may fluctuate in size during the menstrual cycle. They occur less commonly in postmenopausal women unless the woman is on hormone therapy.

Most breast cysts are impalpable and asymptomatic and are an incidental finding on breast imaging. They may present as a smooth and sometimes painful discrete breast lump. A cluster of cysts may present as a tender area of nodularity.

FIGURE 51.3 Breast cyst visible on ultrasound

Cysts have characteristic halos on mammography, and on ultrasound appear as an anechoic lesion with smooth, defined borders and thin capsule with enhancement deep to the lesion, due to the transmission of the ultrasound through the fluid.

Large, painful cysts may be aspirated. The aspirate should be sent to cytology if the lump does not resolve completely with aspiration, if the aspirate is bloodstained or if the cyst has suspicious features on ultrasound, such as internal echoes or an intracystic lesion.

After aspiration, the breast should be re-examined to check that the mass has disappeared. Any residual mass needs full assessment by mammography and non-excisional biopsy to exclude cancer.

BREAST CANCER

BACKGROUND AND PREVALENCE

Breast cancer is the most common invasive cancer diagnosed in women in developed countries and the greatest cause of cancer-related death in women.^1,⁵ There is very good evidence that survival is related to the size and stage of the disease at diagnosis: the earlier the cancer is diagnosed, the greater the chance of effective treatment.^1,⁵

However, even with a fully implemented mammographic screening program, more than 50% of the cancers diagnosed each year will be found as a result of a change in the breast detected by the woman or her doctor. Symptoms of breast cancer include:

• a new or unusual lump/thickening or lumpiness in one breast

• nipple discharge (especially if bloody or serous)

• new nipple inversion or change, such as crusting or ulceration of nipple

• redness, dimpling or puckering of the skin overlying the breast

• unusual and persistent breast pain.

The GP is the first port of call for women with a new breast symptom, the vast majority of which will not be due to breast cancer. The challenge for the GP is to effectively investigate these symptoms and determine those that may be due to breast cancer.

AETIOLOGY

Despite much research into causes and risk factors for breast cancer, we have no means of preventing this disease.⁶ There are a number of factors that bear on the probability of a particular symptom being due to a breast cancer.

In general, breast cancer is a disease of ageing, with 75% of breast cancers diagnosed in women aged 50 years or older, and about 6% in women aged under 40 years. However, breast cancer can occur at any age and it is important that younger women who present with symptoms have these adequately investigated. Other factors that may increase risk for a particular woman include whether she has a significant family history of breast or ovarian cancer ¹ or a relevant inherited gene mutation, whether she has had a previous invasive or in situ breast cancer or a previous biopsy that shows atypical proliferative disease or other marker for increased risk.

A number of other factors associated with risk for breast cancer are not modifiable, such as the age at menarche or menopause. Additionally some potentially modifiable factors are associated with reduced risk but are complex decisions for the individual woman. These include age at first pregnancy, number of children and breastfeeding. However, a number of lifestyle factors affecting risk for breast cancer are readily modifiable.

Lifestyle factors

Alcohol consumption (two or more standard drinks each day) and weight gain after menopause (BMI > 25) have a negative impact on risk, whereas regular exercise has been shown to reduce risk for breast cancer.

All women should be informed of the benefits of a well-balanced diet with low alcohol intake and regular exercise, not only for breast cancer but for other cancers and chronic diseases, and overall good health.

The World Health Organization estimates that 10% of breast cancer worldwide can be attributed to physical inactivity. It has also estimated that about 5% of breast cancers are attributable to alcohol consumption, and that overweight and obesity in postmenopausal women (BMI > 28) increases risk by about 30%.

The risk for breast cancer associated with taking the oral contraceptive pill is small, as the underlying risk for breast cancer is small at the age at which women are generally taking the Pill. The risk associated with HRT increases with increased duration of use, irrespective of the preparation or mode of administration. The decision about starting or staying on HRT must be made by the woman after being fully informed and weighing up the risks and benefits in her individual case.^7,⁸

There are also a number of myths about risks for breast cancer that have no basis in evidence. For example, there is no evidence that wearing underwire bras or using antiperspirant deodorant can increase risk.

PATHOLOGY

The mature female breast contains thousands of potentially milk-producing lobules. Each lobule is drained by a terminal duct attached to the main duct system. Most breast diseases, including cancer, arise from this terminal ductal-lobular unit. About 65% of cancers are invasive ductal, and about 15% are invasive lobular. Tubular, medullary and mucinous breast cancers are less common. About 15% of breast cancers are preinvasive at diagnosis.

The pathological features of the cancer are vital in determining the extent of disease and the potential aggressiveness of the tumour, and in informing treatment decisions.

It is recommended that pathologists provide all relevant information in a synoptic pathology report, such as:

• size

• grade

• margins

• lymphovascular invasion

• hormone receptors

• HER 2

• lymph node status.

DIAGNOSTIC APPROACH

For the GP charged with assessing the presenting symptom, it is important to pursue a systematic approach to investigation that minimises the risk of missing a breast cancer. The ‘triple test’ is universally accepted as the most effective way to maximise the detection of cancer and to provide an accurate diagnosis for an abnormality. The correct sequencing of tests is important to the overall interpretation of the results.

The triple test refers to:

1. taking a history and performing clinical breast examination

2. diagnostic breast imaging, which may be mammography and/or breast ultrasound

3. non-excisional biopsy, which may be fine needle aspiration cytology or core biopsy.

The sensitivity of the triple test approaches 100%. Triple test negative, where no test results are positive (that is, no suspicious or malignant results), provides very good reassurance that the symptom is not due to cancer. Less than 1% of women will be falsely reassured that they do not have cancer, based on correlation of all three test results that are negative.

If any of the tests is suspicious for cancer or malignant (a triple test positive result), or if the results do not correlate with one another, irrespective of whether there are normal or benign test results, further evaluation and referral to a breast surgeon or specialist breast clinic is required.

However, not all women will require investigation with all three tests. Indeed, as the majority of symptoms are due to normal physiological changes, most women will be able to be reassured after providing a history and having a clinical breast examination—for example, where a woman presents with bilateral breast pain that occurs cyclically before her menstrual period and there is no clinical abnormality on examination. Imaging may additionally support this diagnosis.

The sensitivity of each component of the triple test for any individual woman will depend on a number of factors, including the age and history of the patient, the characteristics of the woman’s breast tissue and the characteristics of the breast lesion. For example, the evaluation by clinical breast examination of a small lesion within lumpy breast tissue will be limited; and mammography in a young woman is less sensitive because of the increased density of the breast tissue.

TREATMENT

The vast majority of breast cancers are diagnosed ‘early’—that is, they are confined to the breast with or without local lymph node involvement, and have not metastasised to other organs. The primary goal of treatment of early breast cancer is to control the disease with the aim of achieving cure. The initial management of breast cancer offers the best hope of cure. There are significant differences in women’s views about, and need for, information, choice and support. The patient should be provided with adequate and appropriate information about treatment options in order to make an informed decision about her care.

The way in which a clinician relates to and communicates with a cancer patient can affect her wellbeing.⁹ Communication skills training is available to assist health professionals to manage difficult conversations such as breaking bad news and discussing prognosis.¹⁰

When organising referral for patients with breast cancer, GPs should consider both the preferences of the patient and the fact that patient outcomes are better if treated by clinicians who are part of a multidisciplinary team.¹¹

The usual primary treatment of early breast cancer is surgery. Where appropriate, women should be offered the choice of either breast-conserving surgery followed by radiotherapy, or mastectomy, as there is no difference between them in the rate of survival or distant metastasis. Women who undergo mastectomy should be provided with information about, and the option of, breast reconstruction, either immediate or delayed.

Determining the extent of spread of disease is vital to informing treatment choices. Sentinel node biopsy is increasingly becoming the standard of care for the assessment of the axilla, as it has been shown to be as effective as axillary dissection in predicting lymph node involvement and has less morbidity.

The pathological features of the cancer and the involvement of lymph nodes will provide valuable information to guide decisions about the use of systemic adjuvant therapy, which includes all forms of hormonal and cytotoxic chemotherapy. The aim of this treatment is to treat undetectable remaining cancer and reduce the risk of recurrence.

New targeted systemic therapies, such as tamoxifen for oestrogen receptor positive breast cancer, are constantly evolving and have had a significant impact on breast cancer survival rates over the past two decades. The decisions about adjuvant systemic therapy are most appropriately made in a multidisciplinary setting, and will take into consideration both tumour factors and patient factors such as age and overall health, as well as patient preferences, if known. The suggested treatment plan should then be discussed with the patient such that she has an understanding of the side effects and potential benefits in her individual case. Issues that may affect younger patients’ decision-making, such as infertility and premature menopause, should be discussed and relevant referrals provided if necessary, prior to treatment commencing.

Note that where a woman has had surgery or radiotherapy involving the axillary lymph nodes, thereafter procedures including measurement of blood pressure or venepuncture should be avoided on that side.

Integrative management

Many patients who have been diagnosed with cancer use complementary and alternative therapies as adjuncts to their medical treatment. Most of these patients find this a way of maintaining a sense of control, particularly in relieving side effects of treatment and improving health-related quality of life, as well as facilitating physical and psychological rehabilitation.

Beyond the stage of active medical and surgical treatment and rehabilitation comes the question of enhancing wellbeing and, ultimately, longevity.

It is important to encourage patients to discuss any adjunctive therapies they may be considering or taking during treatment, as some interfere with conventional therapies and may cause harm. Other complementary therapies can work effectively alongside conventional treatment.

Many patients raise the question of antioxidant use during chemotherapy. Despite the concerns of some oncologists, no trials have reported evidence of significant decreases in efficacy from antioxidant supplementation during chemotherapy.¹²

Many of the studies indicated that antioxidant supplementation resulted in either increased survival times, increased tumour responses, or both, as well as less toxicity than controls; however, lack of adequate statistical power was a consistent limitation.

Patients enquiring about using supplements to control radiation side effects should be informed that they must abstain from smoking tobacco if they take antioxidants during radiotherapy.

It is important that patients discuss their motivation for enquiring about antioxidant and other supplement use, and discuss with their oncologist or radiotherapist. It is equally important for oncologists and radiotherapists to provide well-informed, evidence-based advice for patients, rather than a blanket ‘take nothing’.

Hormone therapies for breast cancer can result in a significantly increased risk of cardiovascular disease, obesity, type 2 diabetes, osteoporosis and sarcopenia, so active risk factor management is essential in this group.

General advice includes:

• Encourage a balanced diet with fresh fruit and vegetables and a variety of low-fat protein sources. Include lean organic meat and eggs, fish, tofu, beans. Protein supplements help maintain muscle mass if diet is inadequate.

• Reduce dietary saturated fats.

• Maintain BMI in the healthy range.

• Avoid alcohol.¹³

• Avoid tobacco.

• Exercise, preferably with advice of an exercise physiologist, at least 5 days a week to reduce chronic disease risk factors, overcome side effects of treatment and improve breast cancer survival.¹⁴

• Reduce or eliminate trans-fatty acids, found in commercial processed foods, and use healthy cooking oils such as olive oil or vegetable oil in food preparation.¹⁵

• Establish and maintain a regular routine of adequate sleep.¹⁶

• Avoid HRT for menopause symptoms. Many countries reported significant drops in breast cancer incidence after the sharp reduction in HRT use early this century.^17,¹⁸

Supplements

Supplements may be recommended as adjunctive therapy for nutritional and immune system support, and for reducing the side effects and toxicity of cancer treatment (see ch 24, Cancer).

Beyond the medical and surgical treatment for cancer, patients usually become very focused on measures to improve their wellbeing and longevity.

The individual requirement for nutritional supplements will be determined by the woman’s general state of health, her age, stage of cancer treatment, diet, specific deficiencies and personal preferences.

• A multivitamin¹⁹—daily, containing the antioxidant vitamins A, C, E, the B-complex vitamins, and trace minerals such as magnesium, calcium, zinc and selenium.

• Probiotic supplement—containing Lactobacillus acidophilus, daily for maintenance of gastrointestinal and immune health. Laboratory and animal studies suggest that probiotics may slow the growth of breast cancer cells. However, human studies are needed before we know what role probiotics have in preventing or treating breast cancer.

• Omega-3 essential fatty acids (EFA)—the average Western diet is low in omega-3 EFA. As fish oil, 1–2 g daily.

• Calcium—for bone health, particularly in menopausal women and those on aromatase inhibitor adjunctive therapy.²⁰

• Vitamin D—women who have less exposure to sunlight and have lower levels of vitamin D as a result are more likely to develop breast cancer and other forms of cancer. Vitamin D receptors have been found in up to 80% of breast cancers, and vitamin D receptor polymorphisms have been associated with differences in survival. Although ongoing studies have investigated a possible link between adequate levels of vitamin D and improved cancer prognosis, breast cancer survivors may derive additional, non-cancer-related benefits from adequate vitamin D levels, including improvements in bone mineral density, quality of life, and mood. Maintaining adequate vitamin D stores is recommended for breast cancer survivors throughout their lifetime.²¹

• Melatonin—2–6 mg nocte, for immune support and sleep. Some studies have found that women with lower levels of melatonin, such as those who work night shift or sleep fewer hours, have a higher risk of developing breast cancer. Whether melatonin supplements can help prevent or even treat breast cancer is yet to be determined.²² More research is needed.

• Black cohosh may help to reduce hot flushes in women on tamoxifen and aromatase inhibitors.