Diagnosis of breast cancer

Screening


The aim of screening is to reduce mortality by detecting tumors before they have spread beyond the breast. Screening by regular mammography in 50-65 year olds can reduce the relative risk of mortality from breast cancer by about 18%. The absolute risk reduction is much smaller (0.5%), because the background risk of dying from breast cancer is about 3% in the general population. The trials have not proven an reduction in overall death rate. Overdiagnosis. For every 2000 (some believe this number is 500), women screened for 10 years, 43 cancers would be diagnosed (vs 33 if not screened). This means that 10 additional cancers will be diagnosed, resulting in about 3 fewer deaths (10 deaths instead of 13) from breast cancer. Even though some calculations suggest that this number could be 1 rather than 3, many women may choose to accept the chance of overdiagnosis for the benefit of the small reduction in mortality, particularly if the treatments are made less intrusive. For example, the UK Marmot committee has recommended using a single dose of targeted intraoperative radiotherapy (TARGIT-IORT) concurrent with lumpectomy, which has been found to be as effective for cancer control as several weeks of whole-breast radiotherapy, while reducing deaths from other causes such as cardiovascular and other cancers.
Breast self-examination finds smaller tumors, but not small enough to improve outcomes. Being ‘breast aware’ means one can detect a difference between normal cyclic fluctuations and abnormal changes for which breast specialist advice should be sought.




Signs and symptoms


Although a lump in the breast is the most common presenting symptom of early breast cancer, a variety of other signs and symptoms may be present Cancerous lump is generally single, hard and painless, and may be irregular in shape. Dimpling of skin Very often when a cancer is present, the sign of dimpling of skin can be elicited by raising arms or bending forward. This happens because of infiltration of Cooper’s ligaments (see earlier section), When this is more obvious it can change the shape of the breast as well. Pain in the breast is seldom due to cancer. The most common cause is hormonal changes with the menstrual cycle. In some, it is due to costochondritis (Tietze's syndrome). However, pain does not exclude a cancer. Spontaneous bleeding or clear discharge from the nipple, particularly from a single duct, is an important sign that needs further advice from breast specialist surgeon. The likelihood of cancer is increased if a lump is also present. Enlarged lymph nodes are occasionally the first sign of breast cancer when a one finds a lump in the armpit (axilla) first, and the breast lump may be felt only after the specialist breast surgeon points it out. Differential Diagnosis Although a lump is the first symptom in 80–90% of cases of breast cancer, about 80% of lumps are benign. Benign breast disease affects up to 30% of women; solitary cysts, fibroadenomas, hamartomas, pseudoangiomatous stromal hyperplasia and epithelial dysplasia are some of the common benign breast problems.




Triple assessment


No single test or group of tests provides perfect accuracy in the diagnosis of breast cancer. An ‘index of suspicion’ by a breast specialist surgeon remains the paramount principle. For example, a suspicious mass with negative mammographic findings warrants biopsy; a negative needle biopsy in the same patient should be reviewed for anatomic and histopathological accuracy to ensure that it has been taken from the right place
Clinical examination. A brief guide for professionals: One of the most important questions the surgeon needs to answer is: ‘is there a lump?’ Gentle examination is the key to success, with maintenance of the patient’s dignity always paramount. A thorough examination in various positions is important to elicit some of the important signs of breast cancer. The axillary nodes and supra- and infraclavicular nodes should then be examined by palpation under the arms, above and below the collar bone, and from the front and the back of the patient. Any definite lump must receive a conclusive diagnosis even if an excision biopsy is required to achieve it. Of course, the patient’s wishes about the balance of risks of leaving it alone should be carefully discussed. Frequently, some ‘vague’ lumps disappear when reviewed after 6 weeks at a different time of the menstrual cycle, making any biopsy unnecessary. The color and site of any discharge should be noted and tested for the presence of blood. Discharge from a single duct is usually caused by a duct papilloma; the likelihood of finding carcinoma is about 1%. The patient should also be asked to check if a retracted nipple can be completely everted – as that would reduce any suspicion of cancer. Imaging / Radiology. Mammography and ultrasonography have important roles in the diagnosis of breast cancer. MRI is also useful, particularly when the breasts are dense, and in cases involving a bloody, suspicious nipple discharge or a clinical abnormality such as unexplained skin dimpling. Mammography in someone who has symptoms needs to be considered differently from population screening mammography. Mammography has a diagnostic accuracy of over 95% for clinically detectable tumors, and approximately 50% for subclinical cancers; this falls to about 35% if cancers found only on whole-organ analysis of mastectomy specimens are included. The new technique of tomosynthesis could in theory detect some cancers that are not found on routine single-view mammograms, particularly in mammographically dense breasts. However, tomosynthesis delivers a higher radiation dose than standard mammography and is yet to prove its benefits. As the risk of breast cancer starts to rise with increasing age, a mammogram is recommended for symptomatic women aged 35 and over to try and detect clinically impalpable cancers. Ultrasonography has a specificity of over 95% in distinguishing a solid mass from a cystic mass; it also adds to the sensitivity of triple assessment by detecting mammographically occult cancers. Ultrasound is now used routinely to guide a needle for core biopsy or fine needle aspiration cytology (FNAC) and to localize subclinical lesions with needles prior to excision. Assessment of the axilla is now part of the standard procedure that includes either guided cytology or core biopsy of a suspicious lymph node. Magnetic resonance imaging (MRI), which is based on the nuclear spin of molecules within a powerful magnetic field, is free of ionising radiation. It produces remarkable digitized images that allow three-dimensional reconstruction of the breast. MRI may aid the diagnosis and management of breast cancer in certain clinical situations; for example, in cases of spontaneous nipple discharge, assessment of a breast with nodal involvement but an unknown primary tumor, or screening in patients with a family history or high risk of breast cancer. The downside is that MRI will detect more disease than the observed rate of local recurrence and increases mastectomy rates by up to six times.Randomized trials have found that MRI does not reduce the necessity for reoperation; also, MRI does not change the likelihood of local recurrence or contralateral breast cancer (incidence is 6% with or without preoperative MRI at 8-year follow-up), and does not improve surgical accuracy. It does, however, delay surgery (in one trial, 108 versus 38 days) and detect additional lesions that can prompt more extensive surgery that has been shown to be of no benefit. Therefore, caution should be exercised to avoid ascribing undue importance to ‘latent’ lesions at a distance from the dominant primary, which persuades many surgeons to recommend a mastectomy. Large series have found that patients who underwent breast-conserving surgery after a preoperative MRI (therefore excluding those in whom additional lesions were found) have the same outcome as those who did not have a preoperative MRI evaluation, suggesting that the lesions found on MRI may never have progressed to a clinical tumor. MRI and magnetic-resonance-guided biopsy of the contralateral breast may have prompted an increase in contralateral prophylactic mastectomy, even in cases in which the biopsy was benign. Evidence suggests that such a drastic measure does not save lives, and the availability of a good reconstruction service should not be an excuse for mastectomy of either the breast with the primary tumor or the contralateral side. In a vote by the 2013 St Gallen consensus panel, it was agreed (89.8%) that routine MRI for patients with newly diagnosed disease is not necessary in order to make a decision on breast-conserving surgery. Pathological examinatino of cells or tissue. If a discrete lump is present, and clinical examination and ultrasound suggests that it is a cyst, the fluid can be removed (aspirated) it with a needle and syringe. Aspiration of non-bloody fluid and disappearance of the lump confirms the diagnosis of a benign cyst and the fluid need not be sent for further examination. Such aspiration will provide immediate relief and reassurance. A blood-stained aspirate should be sent for cytological examination and followed by image-guided core biopsy or excision biopsy Core biopsy and fine needle aspiration cytology. A good sampling with image-guided core biopsy is recommended before a lump is confirmed as benign. The clinical and imaging findings should also be concordant. Vacuum-assisted biopsy technique yields more tissue with less chance of missing a cancer, but can lead to bleeding and a haematoma. If the lesion is particularly small, it is prudent for the radiologist to insert a tiny radio-opaque clip at the site of the lesion, as it may be difficult to localize later if cancer is diagnosed. This is particularly important if neoadjuvant systemic therapy is given. If the lesion is too small to be seen on imaging (e.g. < 2 cm) to target with a clinically directed core biopsy, then accurate targeting may be easier using a fina needle aspiration cytology Open biopsy involves the removal of the entire lump under general or local anesthesia, and should only be performed in patients who have been fully investigated by needle biopsy, mammography and core biopsy, and in whom the diagnosis still remains equivocal.




The grade of cancer and stage of disease


Grade and stage tell us quite different from each other. The tumour grade (1, 2 or 3) tells us about the aggressiveness of breast cancer cells. The stage (1, 2, 3 or 4) of the disease tellls us the size of the the breast cancer lump and how far it has spread in the body Tumor grade. The degree of cell differentiation in a tumor can be expressed according to the Scarf–Bloom–Richardson scale, in which glandular formation, nuclear pleomorphism and frequency of mitoses are each scored from 1 to 3. Highly differentiated tumors (grade I, score 3–5) are associated with a better prognosis than poorly differentiated tumors (grade III, score 8–9). Stage of breast cancer. Stage is expressed in terms of TNM - the size of the breast lump / tumour (T), axillary lymph nodes in the armpit or elsewhere (N), and if there is any spread beyond the breast and lymph nodes - called metastasis (M). All combinations of T and N are within stages 1, 2 or 3 when M is M0. When cancer found in other organs, it is M1 and stage 4. Stages 1, 2 and 3 are treated with a curative intent. With modern treatment, stage 4 disease can be controlled for a long time, depending upon the individual case. Routine assessment should include thorough assessment of the breast and axilla with clinical examination and imaging, as well as clinical examination of the neck.




Prognosis: What will be the outcome?


We now have excellent methods of estimating the outcome of individual patients. A historically well-known example is the Nottingham Prognostic Index (NPI), which uses tumour grade, size and number of lymph-node involved with cancer and can be used for assessing prognosis and guiding treatment. Better and more sophisticated web-based tools are now available, such as https://breast.predict.nhs.uk/ Multi-gene expression assays (Oncotype DX, Mammaprint EndoPredict, etc.) either alone or in combination with clinicopathological parameters have improved recurrence prediction and estimates of absolute benefits from systemic therapy, mainly based on the presumption of a constant proportional benefit .




Has the cancer spread beyond the breast?


Routine staging tests to check if the cancer has spread in patients diagnosed with early operable breast cancer are not recommended because such tests are usually negative but can lead to non-specific results and unnecessary anxiety. All national and international guidelines recommend against routine staging for T1–2 and N0–1 disease. If the tumor is large (> 5 cm), or there is extensive lymph-node involvement (e.g. four or more positive nodes), or there are other clinical circumstances then preoperative staging is required (usually CT of the chest, abdomen and pelvis plus a bone scan, or a PET-CT scan).





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