Continuing Education Activity

Breast cancer is a leading cause of cancer-related deaths among females in the world. The rapid growth of breast conservation therapy has significantly changed the management of early breast cancer, with outcomes shown to be equivalent to mastectomy when combined with radiation. This activity reviews the role of breast-conserving therapy in breast cancer treatment. It highlights the role of the interprofessional team in improving care for patients who undergo breast conservation therapy.

Objectives:

• Identify Implthe indications for breast conservation therapy in the management of early-stage breast cancer.

• Determine the preoperative workup, operative steps, and post-operative follow-up for partial mastectomy with axillary lymph node mapping.

• Identify the most common adverse events following breast conservation therapy and associated risk factors.

• Implement interprofessional team strategies for improving care coordination and communication to advance breast-conserving therapy and improve outcomes.

Introduction

Breast cancer ranks among the leading causes of female cancer-related deaths in the world.[1] Surgical management remains the standard of care for noninvasive and localized invasive breast cancer, which may be combined with systemic endocrine therapy, chemotherapy, or radiation. With the publication of the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-06 trial, which showed equivalent disease-free survival, distant disease-free survival, and overall survival amongst women undergoing partial mastectomy with irradiation compared to radical mastectomy, breast conservation therapy (BCT) became standard of care for patients with tumors under 4 cm.[2]

These results received confirmation in multiple studies, including a 20-year follow-up of the NSABP B-06 trial, where partial mastectomy followed by breast radiation continues to be appropriate in the management of smaller invasive breast cancer tumors.[3][4] Additionally, BCT, when combined with radiation, became the standard of care for localized intraductal breast cancers (eg, ductal carcinoma in situ [DCIS]). This development occurred after the NSABP B-17 trial, where the addition of radiation significantly decreased the recurrence rate of noninvasive and invasive breast cancers.[5]

Identified advantages of BCT include reduced operative time, diminished psychological burden when compared with mastectomy, improved cosmetic outcomes, and limited side effects.[6][7] However, other studies have demonstrated no significant difference in depressive symptoms at one year post-operatively between women who underwent a total mastectomy, BCT, and breast reconstruction.[8]

Proper staging is critical for determining the appropriate clinical treatment course and surgical planning. In 2018, the American Joint Committee on Cancer (AJCC) released the eighth edition of the Cancer Staging Manual for Breast Cancer. This staging includes the T (tumor), N (node), and M (metastases) staging, but incorporated biologic markers into the traditional staging system. Factors including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), tumor grade, and multigene assays were included to aid in determining prognosis and therapy as determined by a Clinical and Pathologic Prognostic Stage Group.[9]

Indications

BCT should be a consideration when the surgeon feels that a tumor can undergo excision with clear margins with an acceptable cosmetic result. Adequate margins if there is "no ink on tumor" seen for invasive carcinomas, and 2 mm margins are the recommendation for DCIS.[10][11] Lumpectomy is typically recommended for DCIS/Tis and T1-2 tumors if there are no other contraindications to adjuvant radiation. However, adjuvant radiation results in only a small improvement in locoregional recurrence but not improved overall survival, distant disease-free survival, or breast preservation in patients 70 years old or older with clinical stage I (T1N0M0), ER-positive carcinomas receiving adjuvant tamoxifen.[12] Therefore, the omission of adjuvant radiation in these patients is reasonable.

Contemporary studies have addressed the role of BCT following neoadjuvant chemotherapy for lesions greater than 5 cm. However, tumor size relative to breast size may be more important than exact measurements alone. Evaluation of breast size and discussion with the patient regarding postoperative expectations of her breast size is therefore critical to deciding the best treatment course. Neoadjuvant chemotherapy has demonstrated comparable rates of disease-free survival and overall survival when compared with adjuvant therapy. It may convert patients with large tumors to candidates for breast conservation therapy.[13] In patients with locally advanced tumors who have an excellent response to neoadjuvant chemotherapy, BCT may offer a safe surgical option rather than a total mastectomy.[14]

Male patients have historically received the recommendation to undergo a mastectomy. While this is still the preferred surgical procedure, BCT can be an option in patients with multiple comorbidities or those who desire to preserve their nipple-areolar complex. Although male patients undergoing BCT were less likely to receive standard-of-care therapy, breast cancer-specific survival was not affected by surgery type.[15] However, recommendations typically include adjuvant radiation.

Contraindications

Relative Contraindications

• Prior radiation therapy to the chest wall or breast
• Active connective tissue disease involving the skin (ie, scleroderma)
• Extensive positive pathological margins
• Tumors greater than 5 cm
• Large tumor size relative to breast size
• Known or suspected Li-Fraumeni syndrome (p53 mutation)
• Women with a known or suspected genetic predisposition to breast cancer (ie, BRCA1, BRCA2)

Absolute Contraindications

• First-trimester pregnancy (Radiation therapy is contraindicated during pregnancy; however, pending other treatments needed, BCT is reasonable for some 2nd and many 3rd trimester patients who can receive radiation after delivery.)
• Multicentric disease 
• Diffuse suspicious or malignant appearing microcalcifications
• Extensive DCIS
• Inflammatory breast cancer
• Tumors for which clear margins are unobtainable with lumpectomy with favorable cosmetic results
• Homozygous for ATM mutation

Preparation

Following identification of a concerning lesion on imaging (calcifications or masses), a core needle biopsy of the lesion is preferable over excisional biopsies for optimal surgical treatment. When performed, a small clip gets placed in the biopsy area to confirm the biopsied region and mark the location of concern for future surgical treatments. This clip is especially helpful for lumpectomies for nonpalpable cancers or DCIS that require radiologic identification. Clip placement is crucial in patients undergoing neoadjuvant chemotherapy, as localization of the tumor can become extremely difficult in patients who achieve significant clinical responses. 

The most commonly used approach to this is wire-guided localization. A radiologist or operating surgeon typically performs this procedure on the same day as surgery. Under stereotactic or ultrasound guidance, a wire is inserted through the skin and terminates at the lesion or area of concern.[16] Soft compression mammographic images are obtainable after wire localization confirms the relation of the wire to the suspected lesion for surgical planning. This wire then serves as a guide for surgical excision and gets removed with the surgical specimen.

There are disadvantages to wire-guided localization, including the presence of a foreign body at the pathological assessment, wire transection, migration, patient discomfort, injury associated with wire barbs, and pneumothorax, which have led to the development of alternative localization approaches.[17] Additionally, if the operating surgeon is not performing the localization in the operating room, surgical scheduling may be more difficult as coordination with the performing radiologist is needed. Wireless localization of nonpalpable lesions has, therefore, become increasingly popular. The most common wireless technologies used are markers that use radiofrequency, radar or infrared, or paramagnetic iron oxide. Radio-guided occult lesion localization involves a nonspecific radio-isotope, commonly technetium-99, injected into the tumor and identified intraoperatively with a hand-held gamma probe.[17] This technique has been deemed increasingly feasible. Other less utilized approaches include intraoperative ultrasound-guided resection, cryoprobe-assisted localization, carbon marking, methylene blue dye marking, and near-infrared fluorescence optical imaging.[17]

Technique or Treatment

Following a localization procedure, the surgeon performs the lumpectomy with the patient in the supine position with the ipsilateral arm at 90 degrees. The incision location can be planned either near or distant from the location of the lesion. Incisions may be placed within the Langer lines over the mass when possible and made large enough to avoid excess manipulation when delivering the specimen from the field. A short, curvilinear incision may suffice for small tumors versus a radial incision for large tumors, which may result in less distortion of the nipple-areolar complex. With more emphasis on cosmesis, the use of more conspicuous regions of the breast has become popular, which include periareolar, inframammary, or axillary incisions.

The incision is opened, and dissection is carried down into the breast tissue. Skin flaps are raised in all directions over the mass or area of concern. Sufficient subcutaneous fat should be left in place to provide adequate blood supply to the flaps as they are elevated. Occasionally, the skin may require resection to obtain sufficient margins for superficial lesions or prevent ischemia. Dissection is carried down just above the identified tumor and then completed circumferentially. The tumor is excised with enough surrounding tissue to ensure that inked specimen margins are free of tumor. If needle localization is performed, identification of the thickened portion of the wire allows a better estimation of the lesion location and margins needed. Pectoral fascia and muscle are only removed if required to obtain tumor-free margins. The specimen is oriented before removal from the surgical field with suture or ink. When performed, the specimen is inked on six sides, either by the operating surgeon or a pathologist.

Intraoperative specimen imaging is then typically performed to confirm the location of the biopsy clip, possible marker (wire or wireless), and to ensure adequate margins if the lesion is visible. Mammogram of the specimen is common, although other modalities are also options. The cavity margins are inspected for remaining suspicious tissue. Re-excision of a suspected close margin may be performed by removing another 0.5 cm  to 1 cm of tissue, appropriately oriented for the pathologist. Some surgeons also take "shave margins," where at least an additional 1 mm of tissue gets taken from the cavity. This practice may lower both margin positivity and re-excision rates.[18][19] The cavity is then marked for guiding future radiation. Titanium clips are placed at the superior, inferior, medial, lateral, and posterior margins. Three-dimensional, absorbable markers are also an option, which may provide benefits for radiation guidance and result in overall lower tumor bed volume.[20][21]

Oncoplastic techniques may be utilized to achieve adequate tissue resection and an acceptable cosmetic outcome without the need for breast reconstruction. Oncoplastic surgery is a form of breast conservation that uses volume replacement or tissue displacement techniques to optimize aesthetic results following partial mastectomy.[22] With increasing popularity, several studies have examined the safety of oncoplastic surgery with evidence suggesting a decreased rate of re-excision and improved rate of negative margins,[23][24] psychosocial and aesthetic benefits,[25] and cost-effectiveness.[22] However, patients should be carefully selected and counseled, as tissue rearrangement procedures should be avoided in patients who actively smoke or have significant comorbidities that may impede wound healing or increase a patient's risk for flap or tissue necrosis.[26] Tissue rearrangement can be problematic in the extremely fatty breast. Patients with small breast sizes may also be at increased risk for deformity or decreased cosmetic outcomes. Overall, most studies have shown similar rates of surgical complications amongst patients who undergo oncoplastic surgery vs. standard breast conservation surgery.[27] One single-institution study found that oncoplastic surgery resulted in fewer postoperative seromas compared to standard breast-conserving therapy but noted an increased rate of wound-related complications.[28]

These procedures are categorized as Level 1 and Level 2 procedure types. Surgeons consider Level 1 procedures when excising less than 20% of breast tissue in small-to-moderate-sized breasts. These procedures involve aesthetically placed incisions either at the inframammary crease, periareolar margin, or axilla.[22] Following excision of the specimen, the surgeon creates dermoglandular planes using superficial and deep dissection to fill in the created tissue void; this is performed after marking the cavity for radiation. Examples of Level 1 procedures include local tissue rearrangement, crescent mastopexy, and doughnut mastopexy.

Level 2 procedures are those that require the removal of 20% to 50% of breast tissue in moderate to large-sized breasts with moderate to severe ptosis.[22] Level 2 techniques often involve the development of a pedicle with a circumvertical or wise skin incision pattern. Examples of level 2 procedures include circumvertical mastopexy design and reduction mammoplasty. Breast asymmetry has not shown itself to be a significant issue as a contralateral symmetry procedure during or even after the index operation can be performed. Any procedure requiring the removal of more than 50% of breast tissue merits consideration for volume replacement reconstruction.

Regional lymph node staging is performed in conjunction with breast-conserving therapy. The sentinel lymph node is most likely to contain metastatic disease and is identified and removed via an axillary incision. Identification of the sentinel axillary lymph node uses either a radiolabeled colloid, injection of isosulfane or methylene blue dye, or both. The use of dual tracer has shown to have higher rates of node identification and lower false-negative rates.[29] Further, the need for axillary intervention is determined based on the number of positive nodes as outlined by the ACOSOG Z0011 trial.[30] For patients with T1-T2 tumors with 1 to 2 positive sentinel lymph nodes (without gross extranodal extension) who plan to undergo whole breast radiation, no further axillary surgery is necessary.[30][31]

Complications

Complications of breast cancer conservation therapy include:

• Seroma
• Hematoma
• Fat necrosis
• Infection with the development of cellulitis or abscess
• Altered sensation to the breast or nipple
• Close or positive margins
• Poor cosmetic outcome
• Lymphedema following sentinel lymph node biopsy
• Wound dehiscence, especially in oncoplastic technique; most commonly seen at the inverted T-junction in a wise incision pattern [22]

Clinical Significance

Patients with invasive breast cancer who undergo BCT should receive postoperative whole breast radiation as recommended by the National Comprehensive Cancer Network (NCCN) guidelines. The purpose of radiotherapy is to eradicate any microscopic foci of remaining tumor cells in the conserved breast tissue to prevent local recurrence and distant metastasis. The addition of radiotherapy halved local recurrence rates, and there was an estimated 5% absolute reduction in breast cancer death at 15 years.[7] However, interest in accelerated partial breast radiation, intraoperative radiation, and brachytherapy (with the placement of catheters in the resection cavity) has been increasing.

Additional adjunctive endocrine therapy has its basis on hormone receptor status, which is estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2)/Neu status and is discussed elsewhere. For those patients with triple-negative expression, BCT merits consideration, but chemotherapy is a recommendation.[7][31][7] For patients with a diagnosis of ductal carcinoma in situ, considered to be a precursor for invasive carcinoma, similar considerations are necessary to determine if BCT is appropriate.

Following curative treatment of nonmetastasized breast cancer with breast-conserving therapy, imaging surveillance is of utmost importance to monitor for locoregional recurrence. Bilateral mammography 6 to 12 months after completing radiation therapy, followed by an annual screening mammogram and biannual breast exam, is the recommended procedure.[32] Routine use of annual contrast-enhanced MRI is generally not recommended except in high-risk patients such as those with familial/genetic risk of recurrence, dense breast tissue, and diagnosis under the age of 50.[32] This approach should not replace annual mammography but rather serve as an adjunct, often alternating with mammography for biannual imaging.

Enhancing Healthcare Team Outcomes

Interprofessional oncology teams incorporate a wide range of clinical specialists, including those in surgery, medical oncology, radiation oncology, genetics, pathology, specialist cancer nurses, and oncology pharmacists, to discuss the needs of patients with a confirmed cancer diagnosis. Globally, many healthcare systems address these needs at weekly interprofessional meetings.[33] Nursing is usually responsible for any medication administration accompanying breast-conserving surgery, and the oncology pharmacist will weigh in for checking dosing and agent selection options, working in conjunction with the oncologist and other clinicians.

Retrospective studies have shown improved breast cancer survival rates when treated by an interprofessional team.[34] Moving forward, it is essential not only to continue utilizing interprofessional team meetings but also to optimize team dynamics and productivity to enhance patient-centered care and improve outcomes.

Nursing, Allied Health, and Interprofessional Team Interventions

Nursing interventions for the patient undergoing BCT encompass the preoperative period, immediate postoperative, and long-term monitoring and surveillance of the patient. The most important preoperative action is to obtain arm measurements of the affected side; this provides the healthcare team with a baseline for lymphedema monitoring. Patients often fear lymphedema. Arm measurement is critical to providers but also reassures the patient that they receive close observation to ensure quick action if postoperative swelling does occur. This time also provides an opportunity to teach the patient a gentle range of motion exercises to prevent swelling.  

Secondly, it is crucial to provide thorough education surrounding the operation. Although surgeons do review the procedure and postoperative restrictions, many patients may be overwhelmed at that time. This stress may inhibit the patient, and their family, from thoroughly comprehending the information. A personal, one-on-one conversation can ensure the patient understands the operation. Reviewing the wire or wireless localization is necessary as many patients have a biopsy marker and may not understand why the area needs to be localized. The clinician should also review the purpose of sentinel lymph node biopsy, as many patients misconstrue this, assuming cancer has spread to the lymph nodes.

In the immediate postoperative period, the nurse can address pain control. Education on the dosage of prescription and over-the-counter medication ensures patient safety. If a patient underwent oncoplastic surgery, she must understand that she must refrain from the use of ice on her breast for pain management, as this may compromise wound healing.

During the balance of the patient’s postoperative period, education remains essential. Patients are anxious and eager about the "next step." This patient counsel provides time to review the cadence of treatment and the role of other specialties. The clinician should also take arm measurements beginning at 3 months postoperatively through 5 years to monitor for signs of lymphedema.

Nursing, Allied Health, and Interprofessional Team Monitoring

Clinicians must monitor patients undergoing BCT postoperatively for possible adverse reactions, both immediate and long-term. Immediate monitoring focuses primarily on incision assessment. Clinicians must watch for possible signs of infection, including warmth, erythema, fever, and purulent drainage. They should monitor for swelling as it may indicate a hematoma. Patients should receive instructions to call the office if they develop any of these symptoms. Long-term monitoring includes assessment for signs and symptoms of lymphedema through visual observation and performing arm circumference measurements.