Provincial Health Services Authority (PHSA) improves the health of British Columbians by seeking province-wide solutions to specialized health care needs in collaboration with BC health authorities and other partners.
Reference: (BC Med J 1997;39:496-500)
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Updated February 2016
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About one in nine women living to age ninety will eventually be diagnosed as having breast cancer. Risk increases with advancing age.
3.1 Breast Self-examinationWomen may do regular breast self-examination (BSE). For premenopausal women, this is best done in the week following the menstrual period. For postmenopausal women, a specific day of the month should be chosen.
If done the examination should include inspection of the breast and palpation of the breast and axilla. To perform adequate BSE the patient needs instruction in the technique and the manner in which she is carrying this out. This should be checked at subsequent examinations by her family physician.
There is no evidence that BSE improves survival, but regular self-examination does allow a woman to know her own body and therefore recognize early changes in teh breast texture or appearance. She should be encouraged to bring any concerns to her health care provider.
3.2 Screening Physical Exam by Family PhysicianThe combination of physical examination by a physician and mammographic screening has been shown to reduce mortality from breast cancer. The relative importance of the physical examination vis-a-vis the mammogram remains unclear. It is recommended that all women over the age of 20 years receive an annual physical examination of the breasts by their family physician as a screening procedure. As 10% of breast cancers in older women nad 25-30% of breast cancers in women age 40 to 49 will not be detected by a screening mammogram, physical examination by teh family physician may improve early detection.
3.3 Screening Mammography
The policy of the Screening Mammography Program of BC reflects the latest evidence and our commitment to reducing breast cancer deaths by finding cancer at an early stage. Key policy recommendations are:
Average Risk, Ages 40-49
Health care providers are encouraged to discuss the risks and benefits risks and benefits of screening mammography with asymptomatic women in this age group.
Routine screening mammograms are recommended every two years for asymptomatic women at average risk of developing breast cancer. Patients will be recalled every two years. A health care provider’s referral is not required.
Average Risk, Ages 75+
3.5 Other Methods
There has been considerable interest in methods of detection of non-palpable abnormalities in the breast that do not use ionizing radiation. Such methods include thermography, ultrasound and diaphanography, but in the screening of asymptomatic women none of these techniques approach the sensitivity or the specificity of mammography and cannot be recommended at the present time as the sole screening method.
Ultrasound may be very useful, in conjunction with mammogram, for diagnosis of (to assess) breast lesions, and in that situation is part of the workup of a mass. However, in the absence of any abnormality on physical examination or mammogram, ultrasound is not required, is not a validated screening method, and is not funded.
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Although MRI has advanced some areas of oncologic imaging, as well as neurological and musculoskeletal imaging, the transformation is less complete in breast imaging where other well established and less expensive techniques can often provide necessary information.
The purpose of these recommendations is three-fold, in the absence of substantial randomized controlled trial data on the usefulness and value of breast MRI:
Mammography is the standard breast imaging modality against which other modalities can be judged since there is an extensive body of trial data and a long period of surveillance follow-up. MRI has not yet met the challenge of proving that it can help to decrease mortality, recurrence or impact of treatment. Nor do we know its true positive predictive value. Specificity is variable, particularly in premenopausal women where incidental enhancing lesions are often identified. There is currently no literature of level 1 evidence to support the use of MRI for any specific indication. It is not certain which women or imaging questions will be best served by this modality and at what costs.
Breast MRI should be used in a problem solving mode only after high quality mammography and ultrasound have been carried out. As well, it should be done by a radiologist with expertise in breast MRI, as these images require specialized knowledge for interpretation.
MRI sensitivity rates for the detection of invasive breast cancer are estimated to be as high as 95-100%, which compares well to mammography at 85%. However, a significant limitation is specificity, which is highly variable ranging from 37-97%. Like all breast imaging studies, breast MRI must be correlated with other imaging findings in light of clinical findings.
The Breast Tumour Group (of the BC Cancer Agency) has discussed these indications which have been developed by Drs. Patricia Hassell and Moira Stilwell. The consensus was that as there is not level one evidence we cannot claim that these are standard
Guidelines but are suggested clinical indications and are divided into those that are more established in terms of benefit, those that are not established but may be indicated for specific patients and those that should not be routinely recommended. MRIs within the context of clinical trials should be considered outside of these indications.
Other than cancer indications, breast MRI can be utilized to evaluate silicone implants.
Evaluation of silicone implants
MRI has been shown to be more reliable than CT, ultrasound or mammography for assessment of rupture/integrity/complications of silicone breast implants. The mean sensitivity was 38% for mammography, 59% for ultrasound and 78% for MRI.
Screening of high risk patients – patients with hereditary cancer risk
In patients who have tested positive for mutations of the BRCA 1 and 2 genes or who are at high risk of breast cancer due to a family history of the disease, MRI has been shown to detect cancers before mammography, ultrasound or clinical examination could detect the malignancy. The greater incidence of high grade invasive malignancies in this high risk group does provide the rationale for using MRI as a screening modality in known mutation carriers (including, but not restricted to, BRCA1 and BRCA2) DEL. In these women, screening is done using annual imaging with mammography and MRI concurrently or alternately. In British Columbia, the role of breast MRI screening in high risk women with a strong family history of breast cancer but no known gene mutation is under review. Studies have suggested that ultrasound may also have a role in following these women but recent literature does not support continued ultrasound screening in asymptomatic high risk women. As scientific evidence concerning the role of MRI in patients with biopsy proven ADH or LCIS has shown that although more cancers are detected, this has not yet translated into decreasing mortality, MRI is not used in this situation.
Evaluation of occult breast cancer
In patients with an occult primary presenting with axillary lymphadenopathy or Paget's disease, MRI has been shown to identify the primary in many patients, thus allowing for conservative surgery rather than mastectomy. This is not indicated if mammography clearly shows a suspicious lesion. Trials are ongoing studying the impact of MRI on this group of patients.
B. Possible Uses of Breast MRI
These include a number of clinical scenarios where other imaging modalities have not provided adequate assessment and where a further evaluation with an MRI showing more disease may impact and/or change management.
1. Evaluation of local extent of breast cancer
MRI can be useful in pre-operative assessment of local disease extent when this is unclear either by physical examination, mammography or ultrasound. Mammography is more accurate in determining the size and additional sites of malignancy. However, not all women benefit from having an MRI as 8% underwent additional biopsy or surgery for findings detected on the MRI which subsequently proved to be benign. This may be particularly indicated in lobular carcinoma where mammography may be less sensitive and where there may be multicentric disease.
2. Positive margins – post segmental resection
MRI can be useful in determining the extent of residual disease when margins are positive and the mammogram is not helpful. In the majority of cases however, as further surgery is indicated, it will not necessarily impact on treatment.
3. Post surgical scar vs. recurrent tumor
In cases in which mammography and ultrasound can not conclusively confirm suspected recurrent disease, MRI can be helpful. Breast tissue can show enhancement for up to 18 months following radiation therapy, however. In many of these situations a biopsy will be necessary to rule out disease and may be a preferable diagnostic test.
4. Problem mammogram
MRI can be useful in a small number of patients when there is an equivocal mammographic finding, i.e. a possible architectural distortion, or mass seen only in one view, in whom there is no ultrasound or clinical correlate. Many of these patients have heterogeneously dense breasts.
5. Response to chemotherapy
MRI has been used to monitor treatment response to neoadjuvant chemotherapy in patients with locally advanced cancer. There is controversy over the ability of MRI to determine complete or partial response to treatment. Change in tumor vascularity/enhancement appear to explain changes in functional dynamic contrast assessment and can be seen after only one cycle of chemotherapy. MRI tends to underestimate residual disease. At this time this should only be used in association with a clinical trial.
1. Screening of general population
At present there is no data to support the use of MRI as a screening tool. To date, there are no studies demonstrating decreased mortality by the use of screening MRI. Not all cancers seen on mammography can be identified in MRI. This is especially true for DCIS.
Differentiation of benign vs malignant lesions
Because of an overlap between the enhancement and morphological characteristics of benign and malignant lesions, MRI cannot be used as a substitute for biopsy.
Updated February 2016
Updated February 2016
4.4.2 Breast Cancer Surgical Pathology Reporting
In order to assist with optimal management of patients with breast cancer, the oncologists in British Columbia have requested the following information to be included in pathology reports. For the convenience of the reporting pathologist, the required information is presented in the form of a checklist. This information may be incorporated in the standard report format or may be listed in the form of a synoptic report.
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Side: Right/Left (note - if bilateral please describe each side individually).Specimen Type: FNA, Needle Core Biopsy Surgical Biopsy (incisional/excisional), Wide Excision/ Partial Mastectomy Total Mastectomy +/- sentinel node biopsy/axillary dissectionMeasurement of Specimen: Largest piecePresence or Absence of Tumour Number of Tumours: solitary/ multipleSize of Tumour: 3 dimensions if possibleGross Relationship of Tumour to Margins: measurement to closest marginGross Involvement of Skin or Skeletal Muscle.
Histological Diagnosis: State any specific type of carcinoma.Size: check if greater than gross estimate; use a micrometer if possible. Greatest dimension.Grade: note - see belowLymphatic Invasion Outside the Tumour: Yes/ NoVenous Invasion: Yes/ NoMargins (Invasive ca.):
Distance to Closest Margin State Which Margin If Possible Look for deep fasciaSkeletal Muscle: State If Invaded.Skin:
Dermal Invasion Dermal Lymphatic InvasionNipple:
Paget's Disease Stromal InvasionEstrogen Receptor Status: see belowPR StatusHer-2 neu StatusIntraductal Component:
Present/ Absent Pattern of DCIS (Type) Grade of DCIS EIC Pattern:- Yes /No (note - see below) For DCIS Alone, Measurement of Size is Important. Margin Status - measure distance of DCIS to closest margin. ER status now requiredCalcification in the Tumour (or DCIS): Yes/ NoLymph Nodes:Number of sentinel nodes removedNumber of sentinel nodes positive for metastasesNumber of non-sentinel nodes removedNumber of non-sentinel nodes positive for metastasesSize of Biggest MetastasisExtranodal Extension - measure distance from capsule
Pathological TNM Stage: see below.
Grading System for Invasive Carcinoma of Breast
(I) Nuclear Grade
Nuclear score 1: Nuclei are small to medium-sized, relatively uniform in size and shape, and lacking clumped chromatin or prominent nucleoli. Nuclei may have small, inconspicuous nucleoli. Uniformity of size and shape are the most important features. Nuclear score 2: Nuclei are medium to large in size but exhibit only moderate variability in size, shape and intensity and pattern of staining. Nucleoli may be quite prominent as long as the nuclei are relatively monotonous in appearance. Nucleoli with irregular outlines, giant or "macronucleoli" are absent. Bizarre giant cells are absent. Nuclear score 3: Nuclei are large and vesicular and/or contain coarse clumps of chromatin. There is considerable variation in the size and shape of nuclei. Typically, nucleoli are very large, often multiple and may have irregular outlines. Giant nuclei, polylobated nuclei and multinucleate tumour giant cells may be present. Karyorrhexis, karyolysis and pyknosis of nuclei are often encountered.
Note: The above descriptions are given as guidelines, which may be supplemented by study of illustrations of the different nuclear grades in the references, cited below. Furthermore, since there is a morphological continuum in the nuclear appearance in breast carcinomas, the extremes of the spectrum are easily recognised but, in some cases, the scoring of nuclei is to some extent subjective and differences of interpretation between pathologists are to be expected. It must be stressed that it is impossible to assign a nuclear score based on the frozen section or post-frozen paraffin embedded material.
(II) Tubule Formation
The assessment of tubular differentiation or tubule formation applies to the neoplasm overall and requires examination of several sections at scanning magnification. A reliable tubular score cannot be assigned when only needle biopsies or small pieces of the tumour are examined.
Tubule score 1: >75% of the neoplasm is composed of tubular structures with visible lumina. Solid trabecula, vacuolated single cells, alveolar nests and solid sheets of cells comprise less than 25% of the tumour. Tubule score 2: 10-75% of the tumour has a tubular pattern. Tubule score 3: <10% tubule formation.
(III) Mitosis Score
The mitosis score is assessed in the peripheral areas of the neoplasm and not the sclerotic central zone. The neoplasm is scanned at intermediate magnification to determine the area in which mitoses are most abundant (usually areas of poor tubule formation where cells are arranged in sheets or large nests). Only definite mitotic figures are counted with care to avoid including pyknotic nuclei in the count. Although the Nottingham grading system uses a scoring system based on the number of mitoses per 10HPF's, the Oncologic Standards Committee considers that a mitotic count per square millimetre is most accurate. Mitoses are only counted in the invasive component of the lesion.
Score 1: <4 mitoses per square mm. Score 2: 4-7 mitoses per square mm. Score 3: >7 mitoses per square mm.
Alternatively the number of mitoses in 10 high power fields (HPFs) is counted. Using a Nikon Labophot microscope with a 40X objective lens (i.e. X400) and a field surface area of 0.152mm2, the scores are as follows :-
Score 1: 0-5 mitoses Score 2: 6-10 mitoses Score 3: >10 mitoses
In practice, Contesso's method of scoring of mitoses is quicker and easier to perform especially on small biopsies (e.g. Core biopsies). At least 20HPF's of the same area as stated above are assessed and scored as follows :-
Score 1: No field contains more than 1 mitosis. Score 2: Two mitoses present in any one HPF. Score 3: Three or more mitoses present in any one HPF.
The scores for the three separate parameters (tubules, nuclei and mitoses) are summated and the overall grade of the neoplasm is determined as follows :-
Grade 1: 3-5 points. Grade 2: 6-7 points. Grade 3: 8 or 9 points.
Pathology of Ductal Carcinoma In Situ (DCIS)
The following patterns of DCIS are recognized:
Grading of DCIS
Low Grade (Grade 1): Grade 1 or 2 nuclei and no zonal necrosis.
Intermediate grade (Grade 2): Grade 1 or 2 nuclei with zonal necrosis
High grade (Grade 3): Grade 3 nuclei with or without necrosis
Quantitation: In addition to the maximal linear size of the DCIS, a rough estimate of the volume of DCIS, a relative to the overall tumour should be given as a percentage. "Extensive intraduct component (EIC)" is used to qualify invasive carcinomas with DCIS, which may take two forms as follows :-
This assessment is important because EIC carcinomas treated with breast conservation have a higher risk of local recurrence within the breast unless the margins are well clear (Schnitt 1984).
Grading of Invasive Lobular Carcinoma
In general, it is possible to grade lobular carcinoma. Usually, classical lobular carcinoma will attain a total score of 5 (tubules 3; nuclei 1; mitoses 1) giving the tumour an overall grade 1. Although some of the data are somewhat inconclusive, histological variants of lobular carcinoma are thought to differ in their degree of aggressiveness as follows:
Only invasion of lymphatics beyond the advancing edge of the tumour is important. If in doubt call it negative. Please state if there is extensive lymphatic/vascular invasion (>10 lymphatics involved).
Large calibre, thick-walled blood vessels containing tumour emboli either within the tumour in the surrounding tissue are included.
Neural invasion has been shown not to be of prognostic significance in most studies. This is confirmed in a recent analysis of the BCCA data.
Tumour cells must be outside the nodal capsule. Please state if "minimal" extra nodal spread (<1mm from capsule) or extensive infiltration of perinodal tissues with "matting" of nodes.
Breast markers on invasive carcinoma should be done on the core biopsy sample where relevant. Only if the results appear incongruous with the histology, should the markers be repeated on the excision specimen. DCIS should be stained for ER in the excision specimen. PR and Her2-neu status of DCIS is not relevant for management of the patient.
1) Estrogen Receptors
Please select a block containing invasive carcinoma and normal breast tissue if possible. Immunostains are graded subjectively on a scale 0-3+.
0 :- Negative nuclear staining; positive internal control staining. Allred scores 0(1,2) 1+ :- Allred scores 3-4 2+ :- Allred scores 5 and 6 3+ :- Allred scores 7 and 8
Allred Score: Percentage of nuclei staining + Intensity + Total score
2) Progesterone Receptors: Recommended on all invasive breast cancers.
PR is graded as for ER using the Allred (UKNEQUAS) scoring method.
3) Her-2neu: Required on all invasive breast cancers.
Pathological TNM Stage
The e-book AJCC Cancer Staging Handbook is available online for BCCA Staff. The book is also avaiable from the BCCA Library, or your local health sciences library
Tumour Breast Cancer Staging Diagram
pTX :- unable to assess size. pT1-mic :- <0.1 mm microinvasive pT1a :- Tumour diameter 0.1-5mm pT1b :- 6-10mm pT1c :- 11-20mm pT2 :- 21-50mm pT3 :- >50mm pT4 :- Extension of tumour (any size) to skin and/or chest wall (excluding pec. major muscle).
Nodes – please see official TNM publication for details of complicated classes.
pNX :- Nodal Status Unknown pN0 :- Negative Nodes pN0i+ :- <0.2mm metastases (single cells or isolated tumour cell clusters) pN1mi:- micrometastases 0.2-<2mm diameter pN1a metastases >2mm diameter 1-3 positive nodes N1b Internal mammary LN positive not clinically apparent pN1c Internal mammary SNL +ve (clinically occult) plus 1-3 axillary nodes +ve. pN2a 4-9 axillary nodes +ve. pN2b Internal mammary nodes +ve on micro and clinically. pN3a >10 axillary nodes +ve or infraclavicular nodes +ve pN3b complicated pN3c Supraclavicular node +ve
pMX :- Unknown Status pM0 :- No Distant Metastases pM1:- Distant Metastases Present
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Updated October 2015
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Processing, Reporting and Special Histological Types including Prognostic Factors
Breast Staging Diagram
The major information for staging of breast cancer is derived from the pathology report from teh partial or total mastectomy. However, a full history and physical examination should be undertaken to assess any physical signs and symptoms, which may suggest metastatic disease including assessment of the breasts, axillary and supraclavicular other nodes, especially supraclavicular nodes, lungs, liver and bones. If the physical examination and history are normal and do not suggest metastatic disease, other staging investigations may not be necessary. If there are any abnormal findings these should be further investigated as appropriate.
Patients with clinical stage T1, T2, N0 breast cancer without symptoms of metastatic disease do not require staging investigations, as the yield for these tests in asymptomatic patients is very low. Patients with node positive , T3 or locally advanced disease should have; a bone scan to rule out bone metastases and staging CT scan of the chest and abdomen to rule out lung or liver metastases.
Baseline tumour markers CEA, CA15-3 and CA125 may be considered as part of the initial staging. If normal, they need not be repeated, unless there is a documented recurrence. If they are abnormal, they may suggest metastatic disease, possibly occult. Other than these investigations, prior to chemotherapy a hematology and chemistry panel should be done to rule out bone or liver metastases and to ensure adequate marrow, hepatic and renal function.
Weekly conferences are held (Tuesday AM at the Vancouver Island Cancer Centre; Friday PM at the Vancouver Cancer Centre; Friday PM at the Cancer Centre for the Southern Interior, Monday at noon at the Fraser Valley Cancer Centre and Abbotsford Cancer Centre, and XXX at the Cancer Centre for the North) to discuss the multi-disciplinary management of patients. Diagnostic radiologists, medical oncologists, pathologists, radiation oncologists and surgeons typically attend these conferences. The clinical history, physical examination, pathology slides and diagnostic imaging studies are reviewed and management options are discussed. The family physician and surgeon are welcome to attend any conference when a patient of theirs is being presented.
Patients with breast cancer should be supported in their decision-making about what treatment pathway is best for them. A delay of a few weeks between the diagnosis and definitive treatment has not been shown to be harmful and can allow a one time to gather information and consider his/her options. There are a number of online resources, including a Patient Information Kit that we encourage patients to access. The BCCA
Library has videos, pamphlets and books for loan available to patients provincially - call 604.675.8001 or 1.888.675.8001, local 8001. See also
BCCA Centres and Clinics and
information for patients and the public.
The information in this section of the Cancer Management Guidelines is our current approach to patients with breast cancer. It is not intended to be a comprehensive manual on breast cancer and its treatments nor is it intended to imply that the approach given here is the only acceptable approach. The text, Diseases of the Breast, edited by Harris, Lippincott-Raven, Philadelphia, 4th ed. (2009), is a good source for a more comprehensive discussion of breast cancer.
Referral information for the new patient visit to the BC Cancer Agency
Weekly conferences are held (Tuesday AM at the Vancouver Island Cancer Centre; Friday PM at the Vancouver Cancer Centre; Friday PM at the Cancer Centre for the Southern Interior, Monday at noon at the Fraser Valley Cancer Centre and Abbotsford Cancer Cetnre, and XXX at the Cancer Centre for the North) to discuss the multi-disciplinary management of patients. Diagnostic radiologists, medical oncologists, pathologists, radiation oncologists and surgeons typically attend these conferences. The clinical history, physical examination, pathology slides and diagnostic imaging studies are reviewed and management options are discussed. The family physician and surgeon are welcome to attend any conference when a patient of theirs is being presented.
Patients with breast cancer should be supported in their decision-making about what treatment pathway is best for them. A delay of a few weeks between the diagnosis and definitive treatment has not been shown to be harmful and can allow a one time to gather information and consider his/her options. There are a number of online resources, including a Patient Information Kit that we encourage patients to access. The BCCA Library has videos, pamphlets and books for loan available to patients provincially - call 604.675.8001 or 1.888.675.8001, local 8001. See also BCCA Centres and Clinics and information for patients and the public.
Referral information for the new patient visit at the BC Cancer Agency
People with a suspected diagnosis of breast cancer should undergo initial biopsy, preferably core biopsy, to confirm the pathology. This may be done through medical imaging or in consultation with a general surgeon.
6.2.1 Paget's disease of the Nipple
The standard management of Paget's disease remains surgical excision with either mastectomy or partial mastectomy plus radiotherapy. Since Paget's disease of the nipple is usually associated with an invasive or insitu breast cancer, the breast should be imaged with a mammogram and ultrasound, and if these investigations are non-diagnostic, an MRI of the breast should be considered. Biopsy of the nipple and any suspicious abnormalities found on imaging shoudl be done. A partial mastectomy may be offered for selected patients if breast conservation will lead to negative margins and an adequate cosmetic result. Such patients should be referred to a radiation oncologist for post-operative radiotherapy. A sample of underlying breast tissue should be taken with the nipple to evaluate if an associated in-situ or invasive cancer is present. Axillary staging should be done for those with underlying invasive cancer. Recommendation for systemic therapy is dependent on the pathology of the underlying invasive disease.
6.2.2 Ductal Carcinoma in Situ (DCIS)
Appropriate management of pure DCIS requires detailed mammographic evaluation of the breast to obtain an assessment of the preoperative extent of the lesion. Close cooperation and communication between the radiologist, surgeon, pathologist and oncologist is crucial to ensure adequate local therapy in patients treated with breast conservation.
Axillary dissection is not routinely recommended for patients with pure DCIS because the risk of axillary nodal involvement is <1%. However, the larger the focus of, DCIS the higher the chance a focus of micro-invasive disease is present. Therefore, an axillary lymph node dissection or sentinel node biopsy, may be appropriate in a patient with DCIS >5cm in diameter. All patients with invasive disease should have axillary staging.
Patients with pure DCIS may be treated with mastectomy or breast conserving therapy. Both management strategies are associated with survival exceeding 98%. Radiotherapy reduces the incidence of in situ and invasive breast recurrences after breast conserving surgery by half. Currently, adjuvant radiotherapy is recommended for women with DCIS tumour >1 cm in diameter or comedo carcinoma who are interested in breast conservation, and in all patients with close margins (<5mm) of excision after breast conserving surgery.
Women with well differentiated DCIS (cribriform, solid, papillary) that are <1cm in diameter with complete radiographic and pathologic excision (at least 5 mm of normal breast tissue between foci of DCIS and the inked margins) may be considered for management by wide excision alone. All patients should be referred to the BC Cancer Agency after breat-conserving surgery for an individualized discussion of the risks and benefits of adjuvant radiotherapy. Those treated with mastetomy have a very low risk of recurrence and generally do not benefit from radiotehrapy, although radiotherapy may be considered for very high risk cases, e.g. those with very young age, multiple positive margins, high grade disease, and large tumours.
RT should optimally start once healing from the partial mastectomy is complete and generally within 10 weeks of partial mestectomy. If post-operative problems occur, including hematoma, large seroma, infection, breast edema with erythema, or wound dehiscence occur, the start of RT may be delayed to allow resolution. There is no randomised trial evidence showing detriment to delay the start of RT however, retrospective data from British Columbia shows that there is no detriment to delay up to 20 weeks after BCS for patients with invasive disease, which liely also applies to DCIS. RT planning and prescription is similar to those with invasive disease and are described separately. (See RT SECTION 6.10)
Women with very diffuse areas of DCIS (e.g., >5 cm or greater than or equal to ¼ of the breast on mammogram) have a substantial risk of recurrence, even after partial mastectomy and radiotherapy, and mastectomy is recommended.
There are a number of prognostic models (VNPI, MSKCC) that can be used to estimate the risk of local recurrence considering factors such as age, margin status, nuclear grade, size of the DCIS lesion, but the performance of these models has been variable. In the future, tests using a combination of biomarkers, e.g.tumour gene profiling, may be useful for prognostication.
The use of adjuvant hormonal therapy is somewhat controversial. Adjuvant tamoxifen has been shown in two randomized studies to decrease the occurrence of ipsilateral and contralateral breast cancers in women with in situ disease. This benefit is limited to those patients with ER positive tumours. Neither trial showed an improvement in survival with tamoxifen.
The role of adjuvant aromatase inhibitors is evolving. Preliminary results from a randomized study of adjuvant tamoxifen versus anastrozole in women with DCIS treated with lumpectomy show that anastrozole may lead to a modest decrease in breast cancer events, with no difference in survival compared to tamoxifen.
Adjuvant tamoxifen canbe considered in patients with pure DCIS to decrease ipsilateral and contralateral breast cancer events, although there is no benefit with respect to survival. This benefit must be weighed against the increased risk of thromboembolic events and uterine cancer. Adjuvant tamoxifen should not be considered for women with bilateral mastectomies, those with an increased risk of endometrial cancer or thromboembolic events, those with a life expectancy of <10 years or those who have taken tamoxifen for prevention. If used, the tamoxifen dose should be 20 mg/day for 5 years. Contraindications to tamoxifen are discussed more thoroughly below (Table 2, Section 188.8.131.52 Hormone Receptor Positive Breast Cancer.)
The role of anastrozole may become more prominent as further results from recently completed trials are published.
6.2.3 Lobular Carcinoma In Situ
Use of this term is controversial. Most modern authors regard this as indicating a high risk for the development of infiltrating carcinoma in either or both breasts. The risk for subsequent carcinoma is not confined to the segment of the breast involved by the in situ change. The risk to each breast is approximately equal and approaches fifteen percent within ten to fifteen years. Patients can be given the option of either careful follow up or occasionally, bilateral mastectomy with or without immediate or delayed reconstruction. Tamoxifen was shown to decrease the risk of invasive cancer in women with lobular cancer in situ in the NSABP prevention trial using tamoxifen 20 mg daily for 5 years, although there was no improvement in survival. Tamoxifen can be considered if breast cancer prevention is the primary goal.
Invasive breast cancer requires multimodality management that is specific to the stage of the disease. The majority of patients with invasive breast cancer have ductal breast cancer and, less commonly, lobular breast cancer. While there is a slight difference in the natural history of lobular and ductal breast cancer, patients with these two different pathologies are treated in the same way. The management sections that follow, aside from the section about less common histologies (LINK TO THE section 6.11.3 UNUSUAL PATHOLOGIES), refer in particular to those with invasive ductal or lobular breast cancer.
For most patients it is reasonable to try to achieve an ipsilateral breast tumour recurrence (IBTR) rate of <1% per year. The addition of a radiation boost to the tumour bed reduces the risk of IBTR. However, re-excision to obtain negative margins may reduce IBTR more than using a radiation boost. The use of systemic therapy also minimally reduces IBTR.
Those with positive margins have double the risk of IBTR compared to those with negative margins. Those with positive margins have double the risk of IBTR compared to those with negative margins, and those with close margins (< 2 mm) have a 1.7 x increase in risk of IBTR compared to those with negative margins. Most of the randomized trials of breast conservation with radiation vs mastectomy were in the context of no tumour seen at ink at pathologic examination of the resection specimen, although retrospective studies demonstrate an increased IBTR with both positive or close margins.
There is no evidence that re-excision alters survival compared to radiotherapy boost. The degree of survival impact of either, in the setting of close margins in particular, is expected to be small, or negligible, particularly in the absence of other risk factors.
For patients with a high systemic failure risk (e.g those with numerous positive axillary lymph nodes), it may be reasonable to accept a higher risk of IBTR. It may also be reasonable to accept a higher risk of IBTR in patients for whom further local breast surgery would result in an unacceptable cosmetic result, but for whom there is a strong desire to avoid a mastectomy, or if medical problems preclude further surgery. In these situations, a radiation boost would likely be used, albeit this can also affect the cosmetic outcome.
Guidelines for Re-excision and Radiation Boost following breast-conserving surgery
Timing of Adjuvant Radiotherapy:
Reviewed February 2016
Hormone receptor positive breast cancers express estrogen receptors (ER) and or progesterone receptors (PR, PgR) on their nuclei, as evinced by immunohistochemical (IHC) assay. There are two main immunohistochemical scoring systems used by the province to describe the degree of ER and PR expression. The Allred score is made up of a measure of the intensity of the IHC stain and the percentage of cells which take up the stain for the receptor.1 The maximum score (strongest expression) is 8. A simpler scoring method is often used in which the hormone receptor staining strength is expressed from 0 (no staining) to 3 (strong, ubiquitous staining). Cancers with an IHC score of 0 or an Allred score of 2 or 0 do not benefit from hormone receptor targeted therapy. Cancers with an Allred score of 3 have weak staining in a small percentage of cells, and the benefit of therapy targeted at the receptor is debatable in this setting. An IHC score of 1+ is similar to an Allred score of 3 or 4. An IHC score of 2+ can be considered comparable to an Allred score of 5 or 6, and an IHC score of 3+ would be roughly equivalent to an Allred score of 7 or 8.
2. Hormone therapy
Hormone therapy for five years should be considered for all women with hormone receptor positive breast cancer (estrogen receptor [ER] and/or progresterone receptor [PR] allred score 4-8/8; or 1+ , 2+ or 3+) based on robust large clinical trial data sets establishing a significant survival benefit.2 The absolute benefit depends on both the absolute recurrence risk and the relative strength of hormone receptor expression. The decision to treat cancers with an Allred score of 3 with hormone therapy should be individualized.
2A. Premenopausal women
For premenopausal women, the hormone therapy of choice is tamoxifen (BRAJTAM). An alternative for women with contraindications to tamoxifen is surgical oophorectomy (permanent) or medical menopause (LHRHa; reversible), with or without an aromatase inhibitor (BRAJLHRHT).3 For select low stage, non grade 3 disease, hormone therapy with both tamoxifen and an LHRHa may be an acceptable and/or superior alternative to chemotherapy.4
Duration of therapy:
The current standard of care for most premenopausal women is 5 years of hormone therapy. Women who remain premenopausal after 5 years of tamoxifen may derive a small additional survival benefit from continuing tamoxifen to a total of 10 years.5 Women becoming menopausal near the end of five years of tamoxifen should be considered for extended adjuvant therapy with an aromatase inhibitor for a further 3-5 years, based on evidence of disease free survival and, for node positive disease, modest overall survival benefits.6 When menopausal status is uncertain, extended adjuvant therapy should be with tamoxifen, given that aromatase inhibitors are not beneficial in premenopausal women.
2B. Postmenopausal women
For postmenopausal women, there are several hormone therapy options. They include 5 years of an aromatase inhibitor; 5 years of tamoxifen; and the sequential use over a total of 5 years of tamoxifen and aromatase inhibitor for about 2 and half years each (BRAJTAM, BRAJANAS, BRAJEXE, BRAJLET). Compared with 5 years of tamoxifen, the use of an aromatase inhibitor (for either five years, or for 2.5 years preceded or followed by tamoxifen) is associated with 3% fewer disease free survival events (defined as any of contralateral breast cancer, relapse of prior breast cancer, and death from any cause).7 Despite this, overall survival gains from the introduction of aromatase inhibitors in adjuvant therapy remain elusive.
Menopausal women completing five years of tamoxifen should consider an additional 3-5 years of an aromatase inhibitor or of tamoxifen (if unable to tolerate aromatase inhibitors), depending on the recurrence risk of the original cancer. This is associated with a modest disease free survival improvement over stopping therapy at five years, and for women with node positive breast cancer, a small survival gain.5,6
Ongoing studies are examining whether longer than 5 years is beneficial if the first five years of therapy included an aromatase inhibitor.
The choice of treatment strategy must take into consideration patient co-morbidities and drug side effects, as well as the absolute recurrence risk associated with their cancer. As a guideline, the BC Cancer Agency Breast Tumour group recommends the following:
Table 1. BCCA Breast Tumour Group guidelines for hormone therapy in menopausal non- metastatic hormone receptor positive breast cancer
Tamoxifen for 5 years, unless not tolerated or contraindicated
4+ nodes involved
ER1+ (allred score 3, 4)
Aromatase inhibitor for 2-3 years, then tamoxifen to complete 5 years
Table 2. Contraindications to starting or continuing Tamoxifen
DVT=deep venous thrombosis; PE=pulmonary embolis
Table 3. Contraindications to Aromatase Inhibitors
Table 4. Minimum eligibility criteria for BC funded Oncotype Dx Assay®
Fit for chemotherapy, and fit for chemotherapy, with hormone receptor positive (ER+ and/or PR+) and HER-2 negative
1. Node-negative or N0i+ breast cancer which is hormone receptor positive (ER+ and/or PR+) and HER-2 negative
§ Any grade 3 cancers
§ Grade 2 cancers and T1b or larger
§ Any Grade 1-2 cancers (any size) in women 40 years of age and younger
2. Node-postive (pN1mi only) (0.3-2mm micrometastases in ONE lymph node)
§ Node positive breast cancer
§ HER-2 positive breast cancer
§ Grade 1 cancers in women older than 40 yeasr of age at diagnosis
§ Grade 2 cancers smaller than T1b in women older than 40 years of age
§ Patients unwilling to consider or unfit to receive chemotherapy
§ Patients who have only had core biopsy and not definitive surgery
Updated February 2016
CONTENT CURRENTLY BEING UPLOADED AND REVIEWED
The use of systemic and or radiation therapy prior to surgery (neoadjuvant therapy or NAT) has been studied since the early 1970s1. There are several potential advantages to the use of NAT2:
The key landmark study by Wolmark et al in 2001 (NSABP B-18) demonstrated that NAT (with chemotherapy) was safe, with no difference in outcomes of disease free survival (DFS) or overall survival (OS) in patients who received either pre-operative chemotherapy or post-operative chemotherapy3. It was demonstrated, however, that patients who had a complete pathological response (pCR) to NAT had an improved OS compared to those who did not achieve a pCR with NAT.
NAT has been since studied in multiple settings, tumour subtypes, and with many different types of agents. NAT may be considered in certain patients with early stage breast cancer, and is the standard of care for patients with locally advanced breast cancer or inflammatory breast cancer.
What are the key steps in the pathway of care for patients treated with NAT?
The neoadjuvant treatment of breast cancer requires a coordinated effort amongst surgical oncology, medical oncology, radiation oncology, nursing, pathology, radiology and clerical booking staff. One of the main barriers to use of NAT can be efficiencies in communication amongst all care providers. Strategies to overcome this are currently underway in many centres (see Locally Advanced Breast Cancer Network).
If a patient is felt to be an appropriate candidate for NAT by a surgeon or family physician, an urgent referral should be sent to medical oncology. If a biopsy has not yet been done, a surgical consult may also be required. Radiation oncology should be consulted early in the patient's course, as the breast cancer can change in size and volume dramatically from initial presentation due to NAT.
Work up prior to initial neoadjuvant treatment should preferably include the following: histological confirmation and receptor status (ER, PR, Her2 on the core biopsy specimen; breast imaging; imaging of the ipsilateral axilla with FNA of any suspicious appearing lymph nodes; or FNA of any clinically apparent lymph nodes; clinical staging (accurate tumour measurement on clinical exam); metastatic survey including imaging of the chest, abdomen (in the cases of clinically stage IIB-stage III disease).
Options for systemic therapy are outlined in the section below. After initiation of NAT, patients should be assessed clinically at each cycle (or monthly in the case of neoadjuvant endocrine therapy). Upon re-assessment, clinical measurement of the tumour and lymph nodes should be recorded and compared to the previous cycle. Cancers that are responding should continue the planned treatment protocol. Hormone therapy should be given after completion of NAT if cancer is ER positive (See Systemic Management - Early Breast Cancer in 2.0 Systemic Management - Introduction ). If the cancer is her2 positive, trastuzumab should be given for one year, starting during the non-anthracycline portion of the chemotherapy.
If the tumour enlarges while on NAT, treatment should be changed. Non-cross resistant chemotherapeutic agents, salvage radiotherapy, or surgery are all appropriate options to consider in this setting. Discussion of these cases at a multi-disciplinary tumour board should be considered. Cancers showing equivocal response may benefit the most from tumor board multidisciplinary review, to explore ways to improve clinical response.
Following NAT, patients should undergo definitive local therapy, which usually involves surgery and radiation. Patients with inflammatory breast cancer or locally advanced breast cancer with at least T3 tumours should have a mastectomy. Breast conserving surgery is acceptable for T2 disease if the cosmetic result is felt to be adequate and a clip has been placed prior to NAT to guide the surgeon to the original site of the cancer. If a mastectomy with autologous tissue reconstruction is planned, radiation is generally preferred prior to surgery, to minimize the negative cosmetic effect on the reconstructed breast of radiation. In other circumstances, radiation generally follows surgery. Surgery should be planned for 3-4 weeks following completion of NAT, to allow adequate immune and general recovery first. The typical timelines reported in randomized controlled trials of NAT in breast cancer patients is 3-4 weeks from the last dose of chemotherapy.
Patients with locally advanced breast cancer should undergo axillary dissection, whether or not a sentinel node procedure is done simultaneously. A stand-alone sentinel node biopsy may be appropriate for patients receiving NAT for non-locally advanced breast cancer, depending on their clinical stage.
Patients with technically inoperable tumours after NAT should have radiotherapy after chemotherapy with a view to further local downstaging. If their disease becomes operable, mastectomy and axillary dissection should follow.
Pathology findings following NAT are designated with a 'y' in front of the 'p" (example ypT2N1) to reflect that the cancer has been exposed to treatment. In general, the less disease present, the better the prognosis, with a large jump (improvement) in prognosis occurring with a pathological complete response (pCR).8 The improved disease free and overall survival associated with a pCR has been shown in cancers of all biomarker profiles (triple negative, ER positive, and her2 positive).13
The definition of pathological complete response varies in clinical trials. The strictest definition allows no residual invasive disease or in situ disease in the axilla or breast. The least strict definition considers only the absence of invasive disease in the breast, allowing for residual nodal metastases. The Canadian expert consensus for the definition of pathological complete response is no evidence of invasive disease in the breast or axilla (pan-Canadian consensus 2012). This definition allows for residual DCIS and is consistent with the definition most often reported in clinical trials of NAT.
There is not data to support that additional chemotherapy is of benefit in patients who have residual disease at surgery following NAT. Clinical trial options can be considered if available. Hormone therapy and trastuzumab should be given according to standard of care.
Preoperative chemotherapy (NAT) has several functions:
In general, there is a preference for chemotherapy regimens that include an anthracycline and a taxane, either concurrently or sequentially Chemotherapy Breast Protocols, based on demonstration of improved outcome compared with anthracycline only regimens.14Recommended regimens include BRLAACD and UBRAJACTW, but avoidance of anthracyclines or taxanes, or abbreviated courses, may be necessary for some patients with co-morbidities. Trastuzumab (BRLAACDT) should be added if the cancer is her2+. NAT is typically given for about six months (8 cycles) prior to definitive local therapy, provided there is no adverse progression of the disease on therapy.
The likelihood of achieving a pCR with endocrine therapy is significantly lower than with chemotherapy.
Neoadjuvant endocrine therapy may be an appropriate option in patients found to have hormone receptor positive disease and who are unfit for chemotherapy. Canadian experts from the Canadian Consensus for the Treatment of Locally Advanced Breast Cancer recommend endocrine therapy for patients with ER+PR+Her2- disease and multiple co-morbidities, or who are older than 80 years. The duration of neoadjuvant hormone therapy is not well defined, but studies have been conducted using an interval of 4-8 months.15 The overall goals of care should be discussed with the patient and the duration of therapy should reflect this (ie if the goal is curative then a pre-defined duration of NAT with endocrine therapy followed by surgery; if the goal of care is control then there may be no pre-defined duration of NAT).
Aromatase inhibitors and Tamoxifen have been studied in the neoadjuvant setting.16 In serial biopsy studies, aromatase inhibitors have demonstrated a greater drop in proliferation markers (Ki67) than tamoxifen. Anastrozole, Exemestane, and Letrozole have all demonstrated similar effect on proliferation indices. One study showed better clinical response rates with letrozole than tamoxifen.17 For these reasons, aromatase inhibitors are preferred in menopausal women, although tamoxifen can be used in patients with contraindications or intolerance to AIs.
Hormone Refractory Disease
Inclusion of the internal mammary chain (IMC) node region is controversial. Studies demonstrating a survival impact from regional RT consistently included the internal mammary lymph node region in the treatment volume(14-16). Doing so increases the lung volume treated and for left-sided breast cancer, cardiac exposure. Treatment of the ipsilateral IMC nodal region including the first three inter-costal spaces should be considered when the supraclavicular or axillary nodes are to be treated, and for those with inner quadrant or central tumours.
Updated Februrary 2016
CONTENT UNDER REVIEW
The follow-up of patients who have been treated with curative intent for breast cancer has four main goals:
All patients who have undergone curative treatment for breast cancer should be seen by a physician every 3-6 months for the first 2 years from diagnosis, then every 6 months until 5 years from diagnosis, then annually for a careful history and physical examination including examination of the nodal regions of the head, neck and axilla, breast/chest wall, heart, lung, spine, and abdomen.1 Patients who have not undergone bilateral mastectomy should have annual diagnostic mammography to facilitate early detection of any subsequent new ipsilateral or contralateral breast cancer or recurrence.
Regular history and physical examination plus annual mammography should aid in early detection of local, regional, or distant metastases. In addition to regular follow-up, patients are encouraged to seek medical attention between scheduled visits if they develop unexplained and new, persistent symptoms. In the absence of concerning signs or symptoms, no lab or imaging tests, other than annual mammography, are recommended to monitor for recurrence. Detection of asymptomatic metastases by periodic scheduled investigations has not been shown to increase survival or quality of life.2 Instead, clinicians should maintain a low threshold for promptly investigating any new concerning sign or symptom, even if the likelihood that breast cancer has recurred is low. Patients who have been discharged to their primary care physician for follow up can/should be referred back to their oncologist if concern or confirmation of recurrence arises.
Recurrences of triple negative cancer occur most frequently within the first five years following diagnosis and plateau at about 7 years. Hormone receptor breast cancers continue to recur over time, out to and beyond ten years. Her2 positive cancers that are hormone receptor negative appear to have a relapse pattern similar to triple negative cancers, and those that are hormone receptor positive behave more like their her2 negative, hormone receptor positive counterparts.
Selected recurrences have the potential to be cured with appropriate therapy. These include:
50 g (2 oz)
Milk (skim,1 or 2% MF or whole)
250 mg(1 cup)
Buttermilk, or Chocolate milk
250 ml (1 cup)
175 ml (3/4 cup)
Milk powder, dry
45 ml (3 Tbsp)
Fortified Beverages (soy, rice, orange juice)
15 ml (1 Tbsp)
Sardines, with edible bones
Cottage cheese, 2% MF
125 ml (1/2 cup)
Figs, dried, uncooked
Broccoli, frozen, boiled, drained
Adapted from the Manual of Clinical Dietetics, 6th Edition (p.746-747), by American Dietetic Association et al, 2000.
Calcium intake from all sources should not exceed 2000 mg per day.
Vitamin D (IU)
100 gm (3 oz)
Fish, mackerel or salmon
100 gm ( 3 oz)
Fish, sardines or tuna
Milk or Soy Beverage, fortified
5 ml (1 tsp)
Adapted from the Manual of Clinical Dietetics, 6th Edition (p.746-747), by American Dietetic Association et al, 2000.
Vitamin D intake from all sources should not exceed 4000 IU per day.
Vitamin and Mineral Supplements:
If you can't meet the recommended amounts with food alone, consider a supplement. Calcium carbonate is the least expensive calcium supplement and is well tolerated by most people when taken with food. The absorption of calcium from supplements is most efficient at doses of 500 mg or less. Some calcium supplements also include vitamin D (check the label for the exact amount). A standard multivitamin and mineral supplement provides approximately 175 mg of calcium and 400 IU of vitamin D and other nutrients.
Adequate protein is required to maintain bone health. Include one of the following protein rich foods at each meal: meat, fish, poultry, beans, lentils, nuts, eggs, milk, yogurt and cheese.
Caffeine and salt:
Excess caffeine and salt can have a negative effect on bone. Caffeine is found in coffee and also tea, chocolate (cocoa) and some soft drinks. For optimal bone health, limit coffee to less than 4 cups per day.
Foods high in salt generally include processed foods such as canned soups, snack foods, crackers, pastas and sauces. Check the nutrition label on processed foods and limit salt to less than 2100 mg per day.
Being physically active maintains optimal bone health and decreases the risk of a bone fracture by improving bone mass and increasing muscular strength, coordination and balance and thereby reducing falls. Physical activity that is weight bearing is best, examples include walking, dancing, aerobics, skating and weight lifting.
Smoking is related to poor bone and general health. If you smoke, ask your doctor for assistance to stop smoking.
The literature suggests that pregnancy after a carcinoma of the breast is not hazardous. It is however recommended that patients be advised to delay pregnancy. The length of the delay depends upon two factors, the initial stage of the disease and thus the probability of the development of metastatic disease and the age of the patient at the time of diagnosis.
The greatest incidence of both locoregional recurrence and distant metastases occurs within the first two years following diagnosis and treatment. It would appear that for women in their thirties desirous of a subsequent pregnancy a delay of two years should be recommended. For very young women with breast cancer a delay of five years may be more appropriate since the chance of developing metastatic disease is much reduced after such an interval and child bearing potential is probably not significantly adversely affected. As well, pregnancy while on Tamoxifen is contraindicated. Survivor preferences and medical indications must be balanced for individualized decisions regarding the optimal time to become pregnant after treatment of breast cancer.
These guidelines are based on a review of published data and expert opinion from the Cancerlit and Medline databases (1966-2000) and from recent breast cancer textbooks. The guidelines largely reflect evidence at Levels III-V and sometimes rely on consensus and common sense, due to limited clinical research in this area.
Limitation of shoulder mobility may occur in as little as two weeks following immobilization. Post-operative physiotherapy is useful for most patients.
This guideline applies to the provision of upper extremity rehabilitation, as well as hand and arm care, to prevent/manage symptoms of the upper extremity including decreased range of motion, pain and lymphedema in people who have received axillary surgery as part of the management of breast cancer. Because breast cancer occurs predominantly in women, the remainder of the text addresses women with breast cancer, but recommendations are largely applicable to men as well.
Upper Extremity Rehabilation
Hand and Arm Care
Benefits include functional and timely recovery of the upper extremity and avoidance of lymphedema and/or cellulitis. There may be increased wound drainage if exercises are initiated too early post-operatively (Day 1). However a number of recent studies (Evidence Levels I-II) have supported both the safety and effectiveness of early post-operative exercise. Stretching exercises during the early post-operative period may assist in breaking up of sclerosed lymphatic vessels (which appear as fine, cord-like structures along the medial surface of the upper arm and forearm). Exercises should provide slow, prolonged stretches, particularly to the shoulder abductors and flexors, with minimal pain or discomfort.
To locate a physical therapist in your area who has special expertise in working with women facing breast cancer surgery or recovering from surgery, ask your doctors or women who had breast cancer, or check with the Physiotherapy Association of B.C.. You do not need a doctor's referral to access physical therapy private clinics. The Medical Services Plan of B.C. no longer covers the cost of private physiotherapy treatments unless you meet low-income criteria. Prior to scheduling your first appointment, discuss the costs for the initial assessment, follow-up appointments and cancellation policy.
Recommendations included in these guidelines, for standard pre- and post-operative assessments and treatments under the direction of a physical therapist would likely require fewer than 12 visits. In cases where complications arise, e.g. post-treatment lymphedema, additional physical therapy visits would be necessary. There may also be costs of compression sleeves, compression pumps, and antibiotic therapy in cases of infection. Many of these costs are covered, at least in part, through extended health plans.
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