Abstract
The purpose of this article is to review the current clinical management of in situ breast carcinomas, including how specific aspects of a pathology report are used in clinical decision-making, and to discuss the current role of sentinel node biopsy in management of invasive breast carcinomas and ductal carcinoma in situ of the breast.
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Main
Ductal carcinoma in situ of the breast (DCIS) is diagnosed with increasing frequency as a result of increasing use of screening mammography. The improved image quality obtained with digital mammography techniques has further enhanced identification of calcifications that indicate DCIS. The use of breast MRI has also increased diagnosis of DCIS and can identify areas of DCIS that are not associated with calcifications. Clinical management of DCIS is reviewed in the attached slides and Burstein et al1 have provided an excellent recent review.
Sentinel node biopsy: reducing the morbidity of axillary staging
The pathological status of axillary lymph nodes remains one of the most important prognostic factors in patients with breast cancer. Identification of metastatic tumor deposits in the axillary nodes indicates a poorer prognosis and often prompts a recommendation for more aggressive systemic and local therapies. Surgical staging of the axilla is a routine component of breast cancer treatment for the majority of the 200 000 patients diagnosed with invasive breast cancer in the United States each year.
Unfortunately, axillary dissection is often the main source of morbidity in patients with early-stage breast cancer. Immediate problems include acute pain, the need for hospital stay, reduced range of motion, and the need for a drain in the surgical bed for a week or more. Long-term problems resulting from axillary dissection include permanent lymphedema in up to 35% of patients, numbness in 35%, chronic pain in 10%, and reduced range of motion in 5–10%.2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 An assessment of patients’ subjective symptoms of arm problems shows even higher rates of persistent arm symptoms, with 25–50% of patients reporting arm swelling, pain, numbness, and/or decreased mobility.10, 14, 15, 16 Studies of quality of life in patients treated for breast cancer have shown prolonged decreases in quality of life for those with lymphedema and other chronic arm symptoms resulting from axillary dissection.7, 8, 9, 17
At present, there are no effective therapies to reverse established lymphedema.2 As lymphedema after axillary dissection cannot be ‘cured’, or even reliably prevented, identification of alternatives to standard axillary dissection have been sought.
The technique of sentinel node biopsy was developed with the aim of reducing the morbidity of surgical staging of the axilla. Identification of the first or ‘sentinel’ nodes draining the affected breast using radioactive particles18 or blue dye19 has allowed selective and minimally traumatic excision of only the most informative axillary nodes. Morbidity rates are substantially lower with sentinel node biopsy compared with axillary dissection.6, 17, 18, 19, 20, 21, 22, 23 Acutely, sentinel node biopsy is an outpatient procedure that does not require a drain, allows rapid return to full mobility, and allows return to work weeks sooner than after axillary dissection. Longer-term morbidity is also reduced with a low rate of lymphedema, low incidence of numbness, and low rates of chronic pain.24
Sentinel node biopsy has been shown to provide reliable pathological staging of the axilla, with false negative rates generally <5% in experienced hands.6, 12, 21 Axillary recurrence rates have been shown to be extremely low after a negative sentinel node biopsy without axillary dissection.6, 12 A negative sentinel node biopsy is now widely accepted as sufficient to establish a patient as node-negative, with no further axillary treatment required.
The role of sentinel node biopsy in DCIS
Some authors have recommended routine sentinel node biopsy for DCIS or ductal carcinoma in situ with microinvasion (DCISM), as 8–12% of these patients are found to have nodal metastases on SNB, and up to 20% of patients with DCIS on their initial diagnostic biopsy are upstaged to invasive disease at definitive surgery.
Historically, survival for patients with DCIS and DCISM treated by breast conservation or mastectomy is 97–100%, with deaths presumed to be due to spread of unrecognized or small numbers of invasive tumor cells. In invasive breast cancer, the major role of SNB is to identify patients whose tumor cells have spread beyond the breast, indicating higher risk for systemic disease. It has therefore been suggested to perform in patients with high-risk DCIS, meaning high risk of unrecognized invasive cancer, including those with microinvasion.
Several studies have helped identify sub-groups of patients at higher risk for occult invasive disease. Yen et al25 demonstrated that age ≤55 years, diagnosis by core-needle biopsy, mammographic DCIS spanning ≥4 cm, and high-grade DCIS were independent predictors of invasive cancer on final pathology, whereas only palpable tumor was predictive of a positive sentinel node. Tan et al.26 found that comedonecrosis and diagnosis by core-needle biopsy were independent risk factors for invasion in patients undergoing mastectomy and SNB for DCIS, but found no risk factors predictive for sentinel node metastases.
Although these studies have helped determine which DCIS patients are appropriate candidates for SNB, few have examined the long-term outcomes in patients with sentinel node metastases. Broekhuizen et al27 examined 71 patients with DCIS and 12 with DCIS with <2 mm invasion who had an excision of ≥5 nodes and found that 11/83 had positive axillary nodes by IHC or H&E staining. Of positive lymph nodes, eight contained isolated tumor cells (ITCs), one had micrometastases, and two had macrometastases. At a median follow-up of 102 months, all patients remained free of disease. Moore et al.28 found 43 (9.1%) positive sentinel nodes in 470 patients with high-risk DCIS: 36 with ITCs, 4 with micrometastases, and 3 with macrometastases. Of 25 patients who underwent ALND, only 1 was found to have additional positive nodes. No local recurrences were observed, but one patient with ITCs developed distant metastases at 27 months. Intra et al examined 854 patients with pure DCIS (microinvasion excluded) who had undergone SNB and found 4 with ITCs, 7 with micrometastases and 5 with macrometastases. Of these, 11 patients underwent ALND with no additional positive nodes. At a median follow-up of 41 months, there were two locoregional recurrences and one distant recurrence in patients with positive SNBs. The size of nodal deposits in these patients was not reported.
Murphy et al29 reported a series of 322 patients with DCIS and DCISM and found positive SNBs in 9% of patients, with the majority being pN0(i+). At a median follow-up of 47.9 months there were 13 (4.0%) local recurrences and 1 distant recurrence, all but one in sentinel node-negative patients.
El-Tamer et al30 demonstrated that positive lymph nodes detected by IHC in patients with DCIS did not alter breast cancer recurrence or survival.
Rational use of sentinel node biopsy in DCIS
In the Protocol for the Examination of Specimens from Patients with DCIS of the Breast recently prepared by Lester et al,31 for the Members of the Cancer Committee, College of American Pathologists, it is suggested that patients with DCIS may have lymph nodes sampled in the following situations:
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Extensive DCIS: Patients with extensive DCIS are more likely to have areas of invasion and it may be difficult or impractical to examine all involved areas of the breast microscopically. A lymph node with a macrometastasis would indicate an occult area of invasion.
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Pathological findings based on a previous needle biopsy or excision raising concern for invasion or microinvasion (invasion measuring ⩽0.1 cm in size): If invasion has been documented, the checklist for invasive carcinoma of the breast should be used.
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Imaging findings (eg, an irregular mass) or clinical findings (eg, a large palpable mass) that increase the likelihood that stromal invasion is present.
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Planned mastectomy: The additional sampling of low lymph nodes or a sentinel lymph node does not result in increased morbidity. If the node or nodes are negative, and invasive cancer is found, another surgical procedure for node sampling can be avoided.
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Smith, B. Clinical applications of breast pathology: management of in situ breast carcinomas and sentinel node biopsy issues. Mod Pathol 23 (Suppl 2), S33–S35 (2010). https://doi.org/10.1038/modpathol.2010.53
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DOI: https://doi.org/10.1038/modpathol.2010.53
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