After a diagnosis of in situ or invasive disease is confirmed, definitive surgical planning and attempts to determine cancer stage should ensue ( Table 12.1 ). Preoperative eval- uation for early stage breast cancer requires a thorough history and physical examination, bilateral mammogram, chest X-ray, and routine blood work. A more extensive metastatic evaluation would be indicated in the setting of locally advanced disease, clinically pathological lymphade- nopathy, or concerning systemic symptoms. This could include ultrasound evaluation of the axilla, computed tomography (CT) scan of chest, abdomen and pelvis, or nuclear bone scan. In the absence of such findings, stan- dard surgical planning can continue.
The surgical management of breast cancer has evolved considerably from the time of Halstead with the introduc- tion of the radical mastectomy (surgical removal of the breast, pectoralis major and minor muscles with a full axil- lary lymph node dissection) 10 . Since the early 20th century,
great efforts have been made to obtain not only locore- gional control and long-term survival, but also breast preservation. In 1985, results from the National Surgery Adjuvant Breast and Bowel Protocol (NSABP) B-04 trial demonstrated that total mastectomy with axillary radiation, total mastectomy followed by axillary dissection in the set- ting of regional recurrence, and radical mastectomy had equivalent breast cancer outcomes 11 . Shortly thereafter
the results of National Surgical Adjuvant Breast and Bowel Project (NSABP) B06 were published, establishing the efficacy and safety of breast conservation therapy (BCT) 12 . In fact, a National Cancer Institute consensus
statement was released in 1991 stating that ‘breast conser- vation treatment is an appropriate method of primary ther- apy for the majority of women with Stage I and II breast cancer and is preferable because it provides survival equiv- alent to total mastectomy with axially dissection’. Although the incidence of local recurrence has been reported to be slightly higher for lumpectomy patients in several random- ized series reported 13 , a meta-analysis of nine prospective
randomized trials comparing conservative surgery and radiation with mastectomy showed no survival differ- ences, and an equivalent local recurrence rate 14 .
A patient's desire for and candidacy for BCT must then be assessed. Eligibility for BCT remains a function of the ability to obtain clear surgical margins on the lumpectomy
specimen, the ability to safely deliver radiation therapy, and the likelihood of achieving a cosmetically acceptable result 13 . Generally accepted absolute exclusion criteria to
BCT include multicentric disease, diffuse malignant appear- ing microcalcifications, prior chest irradiation of the pro- posed field, pregnancy, inability to adequately clear margins, and tumor size of more than 5 cm 13 . Recently, breast mag-
netic resonance imaging (MRI) has been gaining increasing popularity as a local staging methodology to help determine BCT eligibility in the setting of a known cancer diagnosis 15 .
Ultimately, it should be noted that patient perceptions, support/peer groups, and treating surgeon's bias clearly can significantly impact a patients choice for BCT 16 .
BCT can be undertaken with or without the aid of wire (needle) localization. The adequacy of lumpectomy is deter- mined by extent of margin clearance and presence of an extensive intraductal component (EIC) of disease. With respect to the former, no general consensus exists. How- ever, several studies have identified a clear margin of 2 mm or more as being associated with an acceptable (7%) rate of local recurrence 17 . Early research suggested that the
presence EIC resulted in unacceptable rates of local recur- rence. More recent studies, however, have demonstrated that when effective margin clearance is obtained, EIC does not increase the likelihood of local recurrence 18 .
Should a patient not meet criteria for BCT eligibility then they should undergo total mastectomy. The evolu- tion of surgical technique for mastectomy parallels that of breast cancer therapy. Remote are the days of the radical mastectomy. Current standards of care endorse the use of skin-sparing mastectomy techniques for those patients desiring reconstruction or traditional total mastectomy for those patients not undergoing simultaneous recon- struction 19 . In either approach the entirety of the breast
mound is removed from its lateral extent at the latissimus dorsi muscle to its superior, inferior, medial, and poste- rior boundaries at the clavicle, inframammary ridge, lateral edge of the sternum, and pectoralis fascia, respec- tively. Careful attention should be given to the thickness of the skin flaps so as not to devascularize the overlying skin while removing macroscopic breast tissue.
Either treatment (BCT or total mastectomy) of the breast pathology, however, needs to be paired with surgical stag- ing of the patient's axilla. With the ever increasing use of preoperative core biopsy this is often accomplished simul- taneously. Because of its ability to provide a focused and accurate histopathological evaluation of the axilla, the sen- tinel lymph node biopsy (SLN) technique has supplanted prophylactic axillary dissection for the purposes of staging at major cancer centers. A recent consensus conference on sentinel node biopsy in breast cancer stated that:
(1) Sentinel node biopsy can accurately stage the axilla and can replace traditional staging with ALND.
Table 12.1 Tumor, node, metastases (TNM) and stage classification for breast cancer
Classification Definition
Primary Tumor (T)
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
Tis Carcinoma in situ
T1 Tumor ≤ 2 cm in greatest dimension
T2 Tumor > 2 cm but ≤ 5 cm
T3 Tumor > 5 cm
T4 Tumor of any size with direct extension to chest wall or skin, includes
inflammatory breast cancer Regional lymph nodes (N)
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in movable ipsilateral axillary lymph node(s)
N2 Metastasis in ipsilateral lymph nodes fixed or matted, or in clinically apparent ipsilateral internal mammary nodes in the absence of clinically evident axillary lymph node metastasis
N3 Metastasis in ipsilateral infraclavicular lymph node(s) or in clinically apparent ipsilateral internal mammary lymph node(s) and in the presence of clinically evident axillary lymph node metastasis; or metastasis in ipsilateral
supraclavicular lymph node with or without axillary or internal mammary lymph node involvement
Regional lymph nodes (pN)
pNX Regional lymph nodes cannot be assessed
pN0 No regional lymph node metastasis histologically, no additional examination
for isolated tumor cells
pN1 Metastasis in one to three axillary lymph nodes, and/or in internal mammary
nodes with microscopic disease detected by sentinel lymph node dissection but not clinically apparent
pN2 Metastasis in four to nine lymph nodes, or in clinically apparent internal mammary lymph nodes in the absence of axillary lymph node metastasis pN3 Metastasis in ten or more axillary lymph nodes, or in infraclavicular lymph
nodes, or in clinically apparent ipsilateral internal mammary lymph nodes in the presence of one or more positive axillary lymph nodes; or in more than three axillary lymph nodes with clinically negative microscopic metastasis in internal mammary lymph nodes; or in ipsilateral supraclavicular lymph nodes Distant metastasis (M)
MX Distant metastasis cannot be assessed
M0 No distant metastasis Stage 0 Tis, N0, M0 Stage I T1*, N0, M0 Stage IIA T0, N1, M0 T1*, N1, M0 T2, N0, M0 Stage IIB T2, N1, M0 T3, N0, M0 Continued
(2) Identification of a tumor-free sentinel node is highly predictive of no additional axillary nodal metastases and no further treatment of the axilla being needed.
(3) Identification of a sentinel node containing metas- tases requires further axillary treatment with either axillary lymph node dissection, axillary radiation, or participation in ongoing clinical trials 20 .
The techniques for sentinel lymph node biopsy are well established and include localization using blue dye (1% isosulfan blue, methylene blue and vital blue dye), radioisotope (technetium-99m sulfur colloid or techne- tium-99m albumin), or a combination of the two. The rate of identification of the sentinel lymph node using accepted SLN technique in experienced hands exceeds 97% 21 . The
need for completion axillary dissection is dictated by gross pathological findings of the sentinel node using hema- toxylin and eosin staining. Current standards call for completion dissection when any gross tumor measuring more than 2 mm is discovered in the sentinel lymph node 22 .
Like surgical techniques, radiation therapy techniques and indications have also become more sophisticated. Radiotherapy remains an integral and essential component of BCT but can vary in its method of delivery. Radio- therapy can be delivered using external beam, interstitial brachytherapy catheter implantation, balloon catheter- based partial breast irradiation, or three-dimensional con- formal techniques. The largest and most established of these remains the external beam modality. External beam principles include the use of tangential photon fields so as to limit visceral organ injury as well as the use of an
additional boost dose to the tumor bed itself, thereby more directly targeting the involved tissue. The efficacy of radiotherapy in decreasing the rate of local recurrence following the surgical treatment of ductal carcinoma
in situ and invasive carcinoma is well established 23 , 24 .
More recently attention has been directed towards the concept of partial breast irradiation. Short-term studies using all three modalities have resulted in rates of local recurrence comparable with traditional whole breast irra- diation 25 . According to a recent consensus statement from
the American Society of Breast Surgeons, a partial breast irradiation is considered most appropriate for patients younger than age 45 with tumors less than 3 cm and who have node negative disease. A large prospective random- ized multi-institutional trial is underway to ascertain the efficacy of partial versus whole breast irradiation, NSABP B-39/Radiation Therapy Oncology Group (RTOG) Study 0319. Reports of success using intraoperative radiation exist 26; however, given the technical and physical
equipment considerations associated with this modality its use remains infrequent.
Depending on a patient's tumor stage and tumor char- acteristics surgical and radiation treatments may be aug- mented by adjuvant chemotherapy or hormonal therapy. This remains a function of tumor size, nodal involvement and hormonal status as well as molecular characteristics. In general, when used in the adjuvant setting, chemother- apy is given to patients prior to radiation treatments, with two exceptions. Patients receiving partial breast irradiation are treated closer to the time of surgical intervention as well as those few patients who are being treated with intraop- erative radiotherapy techniques. Hormonal therapy is commonly not given until all radiation therapy has been Table 12.1 Continued Classification Definition Stage IIIA T0, N2, M0 T1*, N2, M0 T2, N2, M0 T3, N1, M0 T3, N2, M0 Stage IIIB T4, N0, M0 T4, N1, M0 T4, N2, M0
Stage IIIC Any T, N3, M0
Stage IV Any T, Any N, M1
*T1 includes T1mic. From reference 9 .
completed as its concomitant or prior use can increase the rate of radiation recall injuries.
Recent advances in adjuvant treatment have included the expanded use of anthracycline based and taxane based regimens, both of which have been shown to improve disease-free survival (DFS) 27 . Similarly, hormonal thera-
pies have also evolved and are no longer limited to tamox- ifen. Most recently, the aromatase inhibitors have been shown to be superior to tamoxifen in the prevention of recurrence 28 . Currently, ongoing research is attempting to
determine the optimal timing and/or sequencing of tamox- ifen and the aromatase inhibitors therapies. Finally, adju- vant therapies now include targeted molecular strategies, namely trastuzumab which have been shown to improve DFS in selected patient groups 29 .