Multidisciplinary Symposium — Breast Cancer
© International Cancer Imaging Society 2000
Published: 5 May 2015
Contemporary problems in the surgical management of breast cancer: the surgical/radiological interface
Problems with breast-conserving surgery for invasive disease
The morbidity of axillary dissection
The immediate complications of axillary node surgery are relatively insignificant. It is very uncommon for any patient to sustain serious injuries such as brachial plexus nerve or axillary vein injury, and although seroma formation is a very frequent occurrence it is well tolerated and is rarely prolonged. Delayed complications and long-term morbidity are by contrast commonplace and impact on the lives of many individuals. The principle symptoms that may be encountered after axillary surgery are arm swelling, susceptibility to upper limb infections, shoulder stiffness, pain and altered sensation or numbness. Quality of life studies show that lymphoedema is the most troublesome complaint.
Incidence: depends on degree of swelling that is used to define the condition.
Objective arm swelling without symptoms = 40%
Transient early lymphoedema that resolved = 7.5%
Abduction reduced by >15 degrees in 9% at 1 year, other movements unaffected.
Local recurrence following mastectomy approx. = 1%/year (incl. Regional)
Loco-regional recurrence rates in the larger trials of breast-conserving surgery
Effects of local recurrence on survival
Overall survival following local recurrence in breast-conserving surgery is no worse than local recurrence following modified radical mastectomy
Risk factors for local recurrence
Ninety per cent of local recurrences occur in the same quadrant of the breast suggesting that most represent residual disease.
Approx. 10% of patients undergoing breast-conserving surgery can be shown to have adjacent residual areas of multifocal disease
General: local recurrence is more frequent in younger patients and those with larger tumours
Pathological: local recurrence increased with extensive in-situ component, tumour grade and lymphatic/vascular invasion. Nodal status is a possible risk factor.
Problems with breast-conserving surgery for DCIS
DCIS is often extensive in one area of the breast and may be multi-centric. The mainstay of treatment is complete surgical excision. The successful elimination of DCIS represents a chance to avoid potentially fatal invasive disease, but just as with invasive disease the earlier fashion of simple mastectomy has given way to breast-conserving surgery in many patients. A recurrence rate of approximately 1% @ 10 years can be expected after mastectomy compared with 12–20% for breast-conserving surgery. The factors associated with recurrence are the surgical margin, the presence of multifocal or multicentric disease, lesion size and the degree of differentiation of the in-situ change. DCIS is usually not palpable and the pre-operative assessment of extent and multicentricity are problematic given current imaging techniques.
PM studies = 8.9%
15–20% of detected breast malignancy
Distribution in the breast
Holland studied 82 mastectomy specimens in patients with DCIS and correlated the pathology with specimen radiology
DCIS associated with microcalcification in 94% of comedo necrosis and in 53% of micropapillary/cribiform
Histological grade not related to size
12% of comedo necrosis DCIS
44% of micropapillary/cribiform
50% of mixed micropapillary/cribiform+comedo necrosis
True multicentric disease is uncommon — 1/82 breasts (1.2%)
23% DCIS extends through >1 quadrant (90° sector)
33% DCIS measured >40 mm in diameter
i.e. complete surgical clearance difficult in >50%
in comedo DCIS there was a nipple area focus in 64%
in micropapillary/cribiform DCIS nipple area disease in 34%
DCIS involved the nipple itself in half of these cases 70% of disease close to the nipple is mammographically occult
In patients with clear excision margins (>1mm) 43% have residual DCIS.
Relative recurrence rates
Recurrence at 5 years following breast-conserving surgery = 12–22%@5–10 years
Approximately 50% of all recurrences following any treatment modality are invasive and 50% represent further DCIS. Invasive recurrences occur later (2 vs. 5 years)
Cause-specific mortality of those treated by breast conservation = 0–2% @ 10 years
Recurrence rates after breast conservation are approximately halved by radiotherapy
NSABP-24 investigated the recurrence rates following surgery plus tamoxifen. The recurrence rate is reduced but the follow-up is too short to tell whether recurrence is being prevented or just delayed.
Close margins — most studies define ‘close’ as 1 or 2 mm. Risk is particularly high when the margin is <2 mm but decreases progressively with widening margins. By a margin of 10 mm the risk is down to 4% @ 7.5 years[31,34]
Large lesion diameter. As with the measurement of margins this may be very difficult for the pathologist to assess accurately. Areas of DCIS >4–5 cm are associated with high recurrence rates
High histological grade/poor cytological differentiation. Assessment is somewhat subjective. The intermediate grade is particularly inconsistent
Histological evidence of necrosis. This is related to higher histological grade
Atypical ductal hyperplasia or cancerization of lobules adjacent to lesion.
The Van Nuys Prognostic Index (VNPI)
Lesion size Histopathology
<16 mm Not high grade, no necrosis
16–40 mm Not high grade, necrosis present
>40 mm High grade, necrosis present
VNPI = 3 or 4 — low risk of Local recurrence, 3% recurrence @ 8 years
VNPI = 5,6 or 7 — intermediate risk of LR, 23% recurrence @ 8 years
VNPI = 8 or 9 — high risk of LR, 80% recurrence @ 8 years.
Sentinel node biopsy
There is some argument as to how the sentinel node is defined. Theoretically the sentinel node is the node or nodes in each of the sometimes multiple lymph node basins that receives the direct lymph drainage from the site of the lesion. Practically, the sentinel node is the node or nodes in each lymph node basin that receive a blue-stained lymphatic and/or accumulate sufficient tracer to be clearly discernable at surgery. In the case of radioisotope tracers local definitions involving the count ratio of the node and the nodal bed are often used. The ratio has been defined as anywhere between 2 and 10.
Sentinel node biopsy aims to predict the status of the regional lymph node basin draining a carcinoma by analysis of the sentinel node(s) only. There is strong evidence that if the sentinel node is free from metastasis then the rest of the lymph nodes in that nodal basin will also be tumour-free. These sentinel node-negative patients can then safely omit nodal clearance and the morbidity that is associated with it.
In breast cancer approximately two thirds of sentinel node-positive cases have metastases confined only to the sentinel node(s) with all non-sentinel nodes being tumour-free. At the present time patients with a sentinel node containing tumour all undergo further axillary treatment (clearance or radiotherapy).
Site of injection
This varies. The most common is around the tumour. Also popular is sub- or intra-dermal. Occasionally reported into the tumour
alerts the surgeon to drainage outside the axilla;
often shows the presence of multiple sentinel nodes.
Population accuracy = % of cases where the sentinel node biopsy correctly predicts the status of the nodal basin as a whole. (In series with 50–70% node-negative cases the population accuracy can never be worse than 50–70%)
Early (1996–1998) results
Dye & isotope
Recent (1999–2000) results
The figures for the underlying accuracy do not appear in the published results but can be extracted from them. The underlying accuracy represents the number of patients who would benefit most from adjuvant chemotherapy but may miss out on it due to incorrect staging.
Can avoid axillary dissection and the associated arm morbidity in approx. 50–60% of patients with primary breast cancer.
Facilitates the detection of micrometastases
Allows intense histological examination to be concentrated on the sentinel node(s) rather than spread between a large number of non-sentinel nodes. Nodes can be subjected to serial sectioning, immunohistochemistry and reverse transcriptase PCR
Extra axillary nodes
Lymphoscintigraphy has demonstrated drainage to the internal mammary chain in approx. 10% of cases of primary breast cancer
Improved axillary sampling
Sentinel node biopsy can be used in conjunction with axillary node sampling. This ensures that the sample is representative of the rest of the axilla.
There are probably a small number of unavoidable false-negative results. Even when the sentinel node is clearly identified false-negative results seem to arise in approximately 5% of cases. This may be due to an inherent flaw in the convenient sentinel node theory. Current results (see above) indicate a 5–20% false-negative rate in node-positive patients. A small number of node-positive patients may undergo less intensive treatments in error, with potentially fatal results
The more rigorous histological examination of the sentinel node is resulting in ‘up-staging’. This means that there is a larger percentage of node-positive patients in any series (e.g. 29% node positivity increased to 42% when the sentinel node was subjected to more sophisticated analysis). The increase is largely due to the increased detection of micrometastases. The prognostic implications of these small micrometastases is unclear and optimal management will take many years of clinical trials to evaluate
Attempts to analyse the sentinel node by frozen section during surgery have resulted in unacceptable inaccuracy. Presently, the sentinel node biopsy has to be done first and if axillary surgery is required a second operation is necessary
The absorbed dose to the patient is 0.1 mSv
Absorbed dose to surgeon = 2–5µSv per case (maximum dose= 1mSv/year)
Absorbed dose to surgeon’s fingers = 100µSv per case, (maximum dose= 500mSv/year).
Is imaging mandatory for staging?
Mammography is the primary imaging modality in the detection of breast cancer. However, the limited sensitivity and specificity of mammography in the radiographically dense or treated breast and in assessing response to chemotherapy has led to the development of adjunctive imaging techniques including Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET) and Scintimammography (SMM). The role of each of these specialized investigations is yet to be defined, but it has been established that they should not replace the use of conventional mammography and ultrasound, but be reserved as complementary techniques for resolving specificdefined problems. One of their main benefits appears to be improved loco-regional staging. In the current era of breast-conserving surgery accurate staging is mandatory so that inappropriate conservative surgery is not performed. Adjuvant imaging will help define the local extent of disease pre-operatively and thereby reduce local recurrence rates.
In the current era of conservative surgery for early breast cancer it is critical for accurate loco-regional staging to be carried out so that appropriate treatment can be selected. Breast cancer may have a multicentric, multifocal origin; in a radiographic-histologic evaluation of mastectomy specimens, Hollands et al. showed 41% of cases had remote cancer foci most of which were occult at mammography. Tumour size, multifocality, retroareolar tumours and in situ component need to be accurately detected so that optimal local tumour control is made and mastectomy performed as a one-stage procedure if indicated. Flanagan et al. claim mammography to be almost exact in assessing tumour size, but ultrasound tends to be more accurate.
Detection of multifocal tumours and assessment of tumour size by MRI: comparison with conventional imaging
MR mammography as an adjunct to mammography and ultrasound reveals breast cancer with a higher confidence and sensitivity, but with lower specificity. MR imaging-guided needle localization and biopsy systems have been developed to evaluate lesions identified by MR that are clinically and mammographically occult. Cost, lengthy imaging time and poor availability may restrict access to MRI.
Differentiation of benign and malignant breast lesions: MR vs Tc-99m sestamammography[ 17 ]
Whilst both MR imaging and scintimammography are useful in the evaluation of breast cancer, MR was found to be more sensitive and just as specific. MR is a shorter examination time to scintimammography, but claustrophobia in the magnet can often lead to early termination of the procedure. In this instance scintimammography is a good alternative and can also give important information about the axilla. Scintimammography has limited spatial resolution and therefore the size of the tumour affects detection that may account for the low sensitivity. The main problem with scintimammography currently is limited availability as a special prone coil that improves imaging is required. The suggested use of scintimammography is as an adjunct to conventional imaging in failed triple assessment, breast prosthesis and with axillary metastasis and unknown primary.
Failed triple assessment
Negative biopsy of suspicious mass
Axillary nodes with occult primary
Several studies have addressed the imaging of breast cancer with PET. PET produces images that reflect the physiological and biochemical processes of tissues. The most widely used PET pharmaceutical is fluorine-18-fluorodeoxyglucose (FDG) which evaluates the glucose metabolic rates of tissues. Malignancies have exceptionally high rates of glycolysis compared with benign tissues. FDG-PET is suitable for detecting breast cancer and evaluating response to treatment. FDG is taken up by all malignant tissues and therefore whole body scanning can be undertaken with assessment of lymph node involvement and distant metastases. Wahl reported visualization of all 10 primary breast cancers using FDG-PET and Adler showed 96% sensitivity and 100% specificity for the detection of malignancy. A limited number of benign lesions were studied, but these had a lower uptake than malignant lesions. Given the high cost of PET and limited availability, this technique is unlikely to serve as a screening modality for breast cancer. As an adjunct to conventional imaging it can be used in the indeterminate mammogram, prior to biopsy, with axillary metastasis of an unknown primary to search the breast and to evaluate the axilla prior to axillary surgery.
FDG-PET may be used in circumstances where mammography is technically difficult.
Lumpy breasts/ multifocal disease
Assessment of tumour response to chemo-endocrine therapy prior to surgery
Adjuvant systemic therapy following surgery for primary breast cancer with Tamoxifen or chemotherapy can reduce the risk of relapse and mortality. Neoadjuvant chemo-endocrine therapy is also used as primary treatment prior to surgery. Assessment of response to treatment is an important role of imaging in the multidisciplinary approach to treatment of breast cancer.
Changes seen on mammography associated with tumour response include a decrease in size and density of the lesion, calcifications becoming more tightly packed and complete resolution of the lesion. The remaining mammographic lesion may not necessarily contain tumour cells. Ultrasound can be useful in monitoring tumour size and recording changes in Doppler signal. However, even in the presence of no detectable lesion on ultrasound the presence of a viable tumour cannot be eliminated.
MR has recently been reported in the evaluation of response to neo-adjuvant chemotherapy. Gilles assessed residual active disease using dynamic contrast-enhanced MR, and the presence or absence of early contrast enhancement appeared to be a reliable diagnostic criterion for the presence of residual tumour. Abrahams, using rotating delivery of excitation off resonance (RODEO) with gadolinium enhancement, reported that changes in vascularity early in the course of chemotherapy help to predict response. They accurately evaluated residual disease and suggest MR is superior to conventional imaging in the assessment of response to chemotherapy. Conversely Rieber et al. found that post-neo-adjuvant chemotherapy MR led to some false-negatives and an underestimation of residual tumour volume in some, although MR could provide evidence of response after the first two cycles with a high degree of probability.
FDG-PET is valuable for monitoring the effects of pre-operative chemotherapy in patients with locally advanced breast cancer, with better sensitivity for tumour and specificity for nodal metastasis than ultrasound.
Radiation therapy is increasingly being utilized following breast conservation. Post-treatment follow-up is difficult as surgical and radiation changes can mimic recurrence. Mammographic radiation changes are well known and the late phase usually stabilizes by 12 months after completion of radiotherapy. If diagnosed early, recurrences are treated with mastectomy and do not impair survival of these patients. Previously, biopsy was performed to determine whether changes were radiation-induced or a recurrence. Several studies have shown promising results with MRI. FDG-PET and SSM may also have a role in diagnosing local recurrence. Hathaway reported the combined use of MR and FDG-PET and their complementary role: PET identified all cases of metastatic tumour, whereas MR was useful in determining the relationship of the tumour to the axillary and supraclavicular neurovascular structures. Orel reports a high positive predictive value for MR predicting residual tumour after excisional biopsy, which would complement traditional methods of margin evaluation. Patients underwent MR imaging 6–40 days after excision biopsy and results suggest that those with positive margins following surgery should undergo MR to assess for residual disease prior to re-excision.
Imaging plays an important role in loco-regional staging in the current era of breast-conserving surgery otherwise local recurrence rates may be unacceptably high. MR, PET and SSM are being increasingly utilized as adjuvant imaging in loco-regional breast disease and the choice may depend on local availability. PET and SSM are not widely available and, due to increasing access to MR, this may be the favoured technique. MR, PET and SSM should only be used in specific problem-solving areas discussed by the multidisciplinary team. Further studies comparing all three imaging modalities are required.
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