Modern Approaches to the Surgical Management of Malignant Breast Disease

The armamentarium of the modern breast surgeon includes the time-tested procedures of modified radical mastectomy and lumpectomy with sentinel lymph node biopsy with postoperative radiation, but has evolved to include several options that produce excellent oncologic endpoints and improved cosmesis. These options include skin- and nipple-sparing mastectomies with immediate reconstruction as well as oncoplastic procedures that allow larger excisions and better postoperative breast shape. This article provides an overview of these modern surgical approaches for breast cancer treatment.

Key points

  • A variety of surgical approaches exist for the management of breast cancer.

  • Options include breast-conserving surgery, including oncoplastic techniques, as well as mastectomy with a standard, skin- and nipple-sparing approach with reconstruction.

  • Adjuvant therapies such as radiation and systemic treatment (chemotherapy, endocrine therapy) are used in conjunction with surgical management for most patients, dependent on their disease stage and prognostic features.

Introduction

Breast cancer is the second most common malignancy to affect women. In 2017, it is estimated that 255,180 women in the United States will be diagnosed with invasive breast cancer and another 63,410 will be diagnosed with ductal carcinoma in situ (DCIS). Earlier diagnosis and improvements in adjuvant therapy have produced improved long-term survival with lower rates of disease recurrence than ever before. A personalized approach to the management of the disease means individualized decision making regarding not only adjuvant systemic treatments but also surgical and reconstructive choices.

The oncologic goal of breast cancer surgery has been to remove all clinical and radiologic evidence of the disease in the breast and stage the axillary nodes. Over the last 30 years, the surgical techniques used to achieve this goal have changed dramatically. At one time the only choice was whether to remove all (mastectomy) or part (lumpectomy) of the breast in combination with a level I/II axillary clearance. If the breast was conserved, radiotherapy was delivered. Currently, there is an expanded repertoire of surgical procedures designed to extirpate the tumor and achieve optimal cosmesis.

The focus of this article is to review the modern surgical approaches for the management of preinvasive, early-stage, and locally advanced breast cancer (LABC). For each stage, the authors discuss the considerations for surgical decision making and outcomes with breast-conserving surgery (BCS), including oncoplastic approaches, as well as simple, skin-sparing, and nipple-sparing mastectomies with reconstruction.

Introduction

Breast cancer is the second most common malignancy to affect women. In 2017, it is estimated that 255,180 women in the United States will be diagnosed with invasive breast cancer and another 63,410 will be diagnosed with ductal carcinoma in situ (DCIS). Earlier diagnosis and improvements in adjuvant therapy have produced improved long-term survival with lower rates of disease recurrence than ever before. A personalized approach to the management of the disease means individualized decision making regarding not only adjuvant systemic treatments but also surgical and reconstructive choices.

The oncologic goal of breast cancer surgery has been to remove all clinical and radiologic evidence of the disease in the breast and stage the axillary nodes. Over the last 30 years, the surgical techniques used to achieve this goal have changed dramatically. At one time the only choice was whether to remove all (mastectomy) or part (lumpectomy) of the breast in combination with a level I/II axillary clearance. If the breast was conserved, radiotherapy was delivered. Currently, there is an expanded repertoire of surgical procedures designed to extirpate the tumor and achieve optimal cosmesis.

The focus of this article is to review the modern surgical approaches for the management of preinvasive, early-stage, and locally advanced breast cancer (LABC). For each stage, the authors discuss the considerations for surgical decision making and outcomes with breast-conserving surgery (BCS), including oncoplastic approaches, as well as simple, skin-sparing, and nipple-sparing mastectomies with reconstruction.

Ductal carcinoma in situ

DCIS or intraductal carcinoma is a preinvasive nonobligate precursor of invasive ductal carcinoma. Pathologically it can be defined by the presence of malignant epithelial proliferation within the mammary ducts without invasion across the basement membrane. Since the widespread adoption of mammographic screening, detection of DCIS over the last 2 decades has increased 5-fold, now accounting for up to 25% of all new breast cancers. DCIS usually presents as mammographic calcifications; indeed, few women have clinical findings, such as a palpable mass, nipple discharge, or Paget disease of the nipple.

Historically, the surgical management of DCIS involved mastectomy ( Table 1 defines all breast surgical procedures). However, as clinical trials encouraged adoption of BCS for invasive disease, this was reflected in the management of DCIS. From 1985 to 1990, 4 large randomized control trials compared the outcomes of DCIS patients treated with lumpectomy alone versus those who had lumpectomy and radiation (the combined treatment called breast-conserving therapy or BCT). In all of these trials, the addition of adjuvant radiation therapy to lumpectomy produced at least a 50% decrease in ipsilateral breast events (recurrence of DCIS or invasive cancer), with an absolute risk reduction of 15.2% over 10 years (28.1% lumpectomy vs 12.9% BCT). Breast cancer–specific mortality for DCIS treated with lumpectomy, BCT, or mastectomy is extremely low (2%–4%), and there is no prospective randomized study that compares the different surgical options in terms of survival. After BCT, approximately 50% of recurrences are invasive; for these patients, invasive ipsilateral breast tumor recurrence (IBTR) portends a 2-fold increased risk in breast cancer mortality compared with those without local relapse.

Table 1
Breast surgery terminology
Term Definition
Halstead/radical mastectomy Removal of the breast, including complete removal of pectoralis minor, extensive removal of pectoralis major and axillary lymph nodes up to the apex through a large oblique incision reaching the axillary fossa
Modified radical mastectomy (MRM) Removal of the breast and ALND (level I and II) with preservation of pectoralis muscles
Total (TM)/simple mastectomy (SM) Removal of the breast with a large ellipse of skin, including the nipple and areola, without axillary dissection
Skin-sparing mastectomy (SSM) Removal of all the breast, nipple, and areola with preservation of remaining breast skin
Nipple-sparing mastectomy (NSM) or total skin-sparing mastectomy (TSSM) Removal of all the breast with preservation of breast skin, nipple, and areola
Quadrantectomy Excision of a quadrant of breast tissue containing disease, including skin and pectoralis fascia
Lumpectomy Excision of a segment of breast tissue with disease without skin, or muscle; also referred to as partial or segmental mastectomy and BCS
Oncoplastic surgery (OPS) Excision of breast tissue with disease and use of techniques to reshape or rearrange remaining glandular tissue
Axillary node dissection (ALND) Removal of level I (inferior and lateral to pectoralis minor) and level II (posterior to pectoralis minor) axillary lymph nodes
Sentinel lymph node biopsy (SLNB) Removal of the first few axillary nodes that drain the breast: identified by dual mapping using technetium-99m sulfur colloid and blue dye

Most women in the United States will undergo lumpectomy with adjuvant radiation (43%), whereas some will omit radiation (26.5%), with the remaining having mastectomy (23.8%). Patients with estrogen receptor (ER)–positive DCIS may also benefit from endocrine therapy such as Tamoxifen or an aromatase inhibitor if postmenopausal. The NSABP B-24 trial found that women randomized to have 5 years of Tamoxifen (compared with placebo) after BCT showed a 32% reduction in invasive IBTR and contralateral new breast cancers, but there have been no significant reductions in mortality.

The main factors in the choice of surgery for DCIS include the extent of the lesion (relative to breast size) and patient preference. Although most patients present with microcalcifications, the actual area of DCIS may be much larger because there is often multifocal and discontinuous DCIS that is mammographically occult in the surrounding breast. As a result, obtaining adequate margins after lumpectomy may be challenging; a recent Danish study found that patients with DCIS had 3 times higher rates of reoperation for inadequate margins (<2 mm) compared with those with invasive cancer.

The definition of what constitutes an adequate margin for DCIS has historically been controversial. However, a recent, large meta-analysis that included 8651 patients undergoing BCT recommended that a 2-mm margin should be achieved. Wider margins did not confer any further reduction in local recurrence (LR) for women who had postlumpectomy radiation.

Silverstein and Lagios reported a scoring system based on their series of DCIS patients. They suggested that generally older women (>60 years) with relatively small (≤15 mm), lower-grade DCIS with wider margins may avoid radiation, noting a rate of LR at 12 years of 20%. Multi-institutional randomized trials are underway to try to confirm the generalizability of these results and to prospectively define such a low-risk group.

For patients with large lesions relative to breast size, and for those having wide resections with the aim of avoiding radiation, removal of more than 20% of the breast volume may result in a significant cosmetic deformity. In these patients, oncoplastic surgery (OPS), which essentially means a large cancer (onco) excision in concert with reconstructive (plastic) techniques to close the defect and skin while shaping the remaining breast, can provide additional options for a breast-conserving approach. One series used oncoplastic techniques to obtain wide margins around DCIS and, if achieved, has the potential to avoid breast radiation.

Although BCT is an option for most patients with DCIS, some women will need mastectomy because of persistent positive margins, and some may prefer to undergo mastectomy with or without reconstruction in order to minimize local recurrence and also avoid radiation. Using data from the National Cancer Database, Shiyanbola and colleagues found that between 2005 and 2011, there was a significant increase in the use of mastectomy, immediate breast reconstruction, and contralateral prophylactic mastectomy (CPM) for the treatment of DCIS. The type of mastectomy offered to patients depends on patient preference and other reconstructive considerations. Timbrell and colleagues reviewed rates of locoregional recurrence (LRR) of DCIS comparing simple (SM) with skin-sparing mastectomy (SSM). Over a period of 10 years, they found 8/199 patients developed an LRR of invasive breast cancer in the SSM cohort with no recurrences seen in the SM group. Risk factors for recurrence included age less than 50, involved or <2 mm margins and presence of microinvasion.

More recently, nipple-sparing mastectomy (NSM) has been used in selected patients in both the prophylactic and the therapeutic setting. Limited data exist on outcomes for patients undergoing NSM for pure DCIS. However, oncologic selection criteria for NSM for patients with invasive breast cancer historically included smaller tumor sizes (<3 cm) and distance of lesion to nipple of >2 cm. In a large meta-analysis, the risk of LRR was 5.4% after NSM for the treatment of invasive disease. The use of radiation in these studies was quite variable (5.4%–89.7%). Generally, the use of NSMs for DCIS has been restricted to those who present with limited disease distant to the nipple and in smaller breasts without significant ptosis. Since the breast ducts generally open in the nipple and not often in the areola, the authors have, on occasion, removed the nipple and its ducts while sparing the surrounding areola for what might be termed an areola-sparing mastectomy. This procedure is an option for some patients with DCIS that is closer to the nipple itself.

Axillary assessment in the form of sentinel lymph node biopsy (SLNB) is often performed in the setting of mastectomy for DCIS because in approximately 20% of cases, the patient may have underlying invasive breast cancer that was not present in the core-biopsy sampling for diagnosis (especially true for those patients with more malignant-looking calcifications spanning 5 cm or more). For such patients, the SLNB would provide staging information for adjuvant treatment decisions. There is no role for axillary lymph node dissection (ALND) in the management of DCIS.

Early-stage breast cancer

Most breast cancers are classified as invasive ductal (80%) or invasive lobular (10%) carcinomas, with a small percentage being of a special type (commonly tubular, medullary, mucinous, papillary, and cribriform). They are also characterized by intrinsic molecular subtypes, which are defined by genomic criteria but approximated by hormone receptor status (estrogen, progesterone), presence of Her2-neu amplification or overexpression, and often including markers of proliferation ( Table 2 ). This disease heterogeneity dictates adjuvant therapy decisions and accounts for differences in response to systemic and perhaps local treatments. For the purpose of this article, patients with early-stage breast cancer are defined as those who are clinically stage 1 or 2 at initial presentation, and this group will represent approximately 75% of those women diagnosed with invasive disease in 2015. This includes patients with tumors under 5 cm and few (1–3) or no nodal metastases and those node-negative patients with tumors that may be greater than 5 cm (stage I, II).

Table 2
Breast cancer subtypes
Classification/Subtype Clinicopathologic Criteria
Luminal A ER and/or PR+
Her 2 negative
Ki-67 low
Luminal B–Her 2 negative ER and/or PR+
Her 2 negative
Ki-67 high
Luminal B–Her 2 Positive ER and/or PR+
Her 2 overexpressed/amplified
Any Ki-67
Her 2 enriched ER and PR−
Her 2 overexpressed/amplified
Triple negative ER and PR−
Her 2 negative
Data from Goldhirsch A, Wood WC, Coates AS, et al. Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2011. Ann Oncol 2011;22(8):1736–47.

The surgical treatment of invasive breast cancer has evolved significantly over the last century on the basis of large-scale trials. Halstead’s radical mastectomy was largely abandoned after the 10-year results of the NSAPB-04 study were published in 1985. This study, which started in 1971, randomized more than 1700 women with breast cancer to undergo radical mastectomy versus total mastectomy or total mastectomy and radiation (clinically node-negative group) or radical mastectomy versus total mastectomy and radiation (node-positive group) and found no significant difference in disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) between the treatments after 25 years. Putting to rest the Halstedian paradigm extolling the need for radical local-regional surgery paved the way for the introduction of BCS as an alternative surgical approach. Also termed lumpectomy, partial mastectomy, or segmental mastectomy (see Table 1 ), BCS involves preserving the normal-appearing breast tissue and excising the tumor with clear margins. The NSABP-B06 study randomized 2163 patients to total mastectomy, lumpectomy, or lumpectomy and radiation; all patients had an axillary node dissection, and adjuvant systemic therapy was given to those patients with involved lymph nodes. There were no differences in DFS, DDFS, or OS over 20 years of follow-up, as long as tumor-free margins had been achieved in the BCS. Over the next decade, 5 additional international randomized trials compared BCT (BCS + radiation) to mastectomy for early-stage breast cancer and found no difference in OS or DFS between the groups. Although it is important to note that mastectomy does not preclude the risk of local and regional relapse, recent studies show that the rates of local relapse continue to decrease with better and longer systemic adjuvant therapies that are influenced by the individual tumor characteristics, improved pathologic margin assessment, and radiation techniques.

Role of Adjuvant Therapy in Breast-Conserving Surgery: Radiation, and Systemic Therapy

Ten randomized controlled trials have compared BCS with BCS + radiation, all showing the addition of radiation significantly decreased local recurrence by 66%. Thus, there are very few patients who do not benefit from the addition of radiation to BCS.

Although a detailed review of systemic therapy is not in the scope of this article, a brief overview of the approaches to chemotherapy, endocrine therapy, and targeted therapy is depicted in Table 3 . Molecular gene profiling tests such as Oncotype DX for early-stage breast cancer have shown that patients with favorable disease as determined by the “recurrence score” do well in terms of the rate of both local and systemic recurrence. In the TAILORx study, patients with T1/2, node-negative, ER+ve, Her 2–ve breast cancers and recurrence scores less than 11 on Oncotype DX had very low 5-year risk of distant recurrence (<1%) and excellent OS (98%). Current widespread adoption of these tests has changed the landscape for systemic therapy recommendations, which are now more reflective of personalized risk for breast cancer recurrence.

Nov 21, 2017 | Posted by in Dental Materials | Comments Off on Modern Approaches to the Surgical Management of Malignant Breast Disease
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