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A 34-year-old Hispanic woman with no significant medical or surgical history presents to the surgical oncology clinic with a 5-year history of feeling a lump in her left breast, with skin changes that have worsened over the past 6 months.

The patient states that she detected the lump in her left breast 5 years ago. At the time, she had a mammogram that indicated dense breast tissue but was otherwise negative for suspicious findings. She was advised to monitor the lump in her left breast and to seek medical evaluation immediately if there were any changes. Six months ago, she noticed areolar skin thickening and nipple retraction in her left breast, which prompted her to seek further evaluation.


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The patient started menarche at age 13, was on oral contraceptives for approximately 2 years, and is a nonsmoker. A 12-point review of systems is negative except for the presenting symptoms.

Physical Examination

The patient is well-nourished, well-groomed, alert and oriented × 3, and appears to be in no acute distress. She is 167.64 cm (66 in) tall and weighs 73.2 kg with a BMI of 24.2. Her vital signs are unremarkable: heart rate, 70 beats per minute; blood pressure, 118/72 mmHg; temperature, 98.2 °F; respirations, 16 breaths per minute; and oxygen saturation as measured by pulse oximetry, 99% on room air.

Her breasts are examined in sitting and supine positions. The left breast is fuller and sits slightly higher than the right. Left nipple retraction with significant periareolar skin thickening is noted. A large, 8-cm, mobile palpable mass occupies the entire upper outer quadrant and central left breast. A palpable left axillary lymph node, measuring approximately 1.5 cm, is present. There is no discrete mass palpable in the right breast, and no palpable right axillary nodes are found. Physical examination is negative for cervical, supraclavicular, and infraclavicular lymphadenopathy bilaterally. Her cardiopulmonary, musculoskeletal, and neurologic examinations are unremarkable.

Diagnostic Workup

A bilateral diagnostic mammogram is ordered instead of a screening mammogram because the patient has abnormal clinical findings. This imaging indicates a 2.0-cm irregular mass 9.0 cm away from the nipple at the 1-o’clock region associated with fine pleomorphic calcifications in the left breast (Figure 1). The total suspicious area of volume on mammography measures approximately 6.0 cm × 5.0 cm × 4.4 cm and is associated with skin thickening. A 1.0-cm oval mass with circumscribed margins and associated course calcifications is found in the subareolar region of the right breast.

Figure 1. Left. Cranial caudal diagnostic mammogram image of the left breast indicating a 2.0-cm irregular mass located 9.0 cm away from the nipple at the 1-o’clock region that is associated with pleomorphic calcifications. Right. Lateral medial diagnostic mammogram image of the left breast indicating an irregular mass associated with pleomorphic calcifications.

A bilateral breast ultrasound indicates a conglomerate of masses measuring approximately 5.0 cm × 3.3 cm × 1.8 cm located 6.0 cm away from the nipple of the left breast (Figure 2). Several other smaller masses and areas of ductal dilatation extending from these masses to the base of the nipple are found. In total, the measurable disease on ultrasound was approximately 7.0 cm. Associated left nipple flattening and skin thickening measuring 0.5 cm are noted. On the right side, ultrasound reveals a mass measuring 1.0 cm × 0.9 cm × 0.9 cm most consistent with a fibroadenoma. A second, smaller mass, measuring 0.8 cm × 0.7 cm × 0.4 cm, also likely represents a fibroadenoma. These findings correlate to the oval circumscribed mass in the right breast on mammogram.

Figure 2. Left. Long-view axis via ultrasound indicating a conglomerate of masses in the left breast at the 12-o’clock position. The masses measure approximately 5.0 cm × 3.3 cm × 1.8 cm and are located 6.0 cm away from the nipple of the left breast. Right. Blood flow to the mass in the left breast.

Four suspicious-appearing nodes involving the left axillary levels 1 and 2 are found, the largest of which measures 2.1 cm × 1.5 cm × 0.9 cm (Figure 3). No axillary level 3, internal mammary, or supraclavicular adenopathy are found.

Figure 3. Left. Long-view axis via ultrasound indicating suspicious node involving the left axilla at level 1. The node measures 2.1 cm × 1.5 cm × 0.9 cm. Right. Transverse view axis via ultrasound indicating a suspicious node involving the left axilla at level 1.

Pathology results from an ultrasound-guided core biopsy of the left breast at the 12-o’clock position with marker clip placement indicate invasive ductal carcinoma that is histologic grade 3, estrogen receptor-negative, progesterone receptor-negative, ERBB2 (formerly HER2)-negative, and Ki67 54%, with several foci of lymph vascular invasion. An ultrasound-guided, fine-needle aspiration with clip placement of the 2.1-cm left axillary lymph node indicates metastatic adenocarcinoma consistent with primary breast carcinoma.

A bone scan of the whole body and CT of the chest, abdomen, and pelvis with contrast is performed before chemotherapy to rule out distant disease. These studies show no evidence of metastases.

Although the patient does not have a family history of breast cancer, genetic testing was indicated per National Comprehensive Cancer Network guidelines because she is younger than 60 years with triple-negative disease. Genetic testing results are negative.

Oncofertility consultation is offered because the patient is of childbearing age and chemotherapy may induce ovarian failure. The patient declined this consultation.

To address psychosocial support, the patient meets with a social worker and is referred to support groups during her treatment. She also has a nurse navigator to educate her on the various teams involved in her care and what to expect at each appointment. The nurse navigator remains available as a resource for the patient during and after treatment.

Treatment Course

Treatment options such as chemotherapy, radiation, and surgical intervention are discussed with the patient. Based on her clinical stage of cT3cN1cM0 and triple-negative profile, chemotherapy is initiated before surgical intervention. Port placement is recommended for the patient before treatment with doxorubicin and cyclophosphamide for 4 cycles every 3 weeks followed by paclitaxel for 4 cycles, with 3 weekly treatments per cycle. The following laboratory evaluations are performed before each cycle of chemotherapy treatment: complete blood cell count with differential, blood urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total bilirubin.

A cold cap is ordered for the patient to decrease risk for hair loss. Cold caps are recommended to wear approximately 1 hour before the infusion, during the infusion, and at least 3 hours after the infusion for each treatment cycle. Ondansetron 8 mg, prochlorperazine 10 mg, and dexamethasone 4 mg as needed are prescribed to manage nausea during treatment.

Approximately 4 weeks after completion of chemotherapy, the patient undergoes a left modified radical mastectomy to remove the entire left breast and level 1 and 2 axillary nodes in the same surgery as 2 separate specimens. Magnetic seed localized excision is performed as part of the complete axillary dissection to ensure removal of the biopsy-proven and clipped left axillary lymph node.

The pathology results from the left breast mastectomy show rare atypical cells consistent with focal residual carcinoma cells in the background of extensive treatment effects. No lymphovascular invasion is identified. Usual ductal hyperplasia, fibroadenomatous change, stromal fibrosis, and focal microcalcifications are noted. The margins are clear, with distance from closest margin greater than 10 mm anteriorly and superiorly (Figure 4).

Figure 4. Pathology specimen obtained after a total left breast mastectomy showing clear margins, with distance from closest margin greater than 10 mm on the superior and anterior sides. All clips are located within the specimen.

Pathology of the left axillary lymph node with 1 magnetic seed indicates metastatic carcinoma with a metastatic focus of 3 mm without extranodal extension. Level 1 left axillary dissection contents indicate metastatic carcinoma with treatment effects in 2 of 21 lymph nodes, with the largest metastatic focus measuring 1.8 mm without extranodal extension. Left axillary dissection of level 2 nodes indicates metastatic carcinoma in 1 of 3 lymph nodes, with metastatic focus measuring 0.7 mm without extranodal extension.

Postmastectomy radiation is recommended for this patient to decrease the risk for disease recurrence in the setting of advanced node-positive disease. The patient starts physical therapy on postoperative day 14 to improve her range of motion, which decreased because of surgery, and allow her to initiate radiation therapy within 4 to 6 weeks. The patient is scheduled for simulation to prepare for radiation treatment of 50 gray in 25 fractions to the chest wall and regional lymphatics followed by 10 gray boosts to the chest wall. The patient is asked to stop taking vitamin C during radiation treatment because that can decrease the effectiveness of radiation therapy. It is recommended that the patient start capecitabine for 6 cycles during radiation therapy to further reduce her recurrence risk.

Discussion

Triple-negative breast cancer is an aggressive type of breast cancer that is negative for estrogen, progesterone, and ERBB2 receptors, making targeted therapy difficult. An estimated 281,550 new cases of female breast cancer and an estimated 43,600 deaths because of female breast cancer are expected in the United States in 2021.1

Triple-negative breast cancer has an incidence of 13.2 per 100,000 women and accounts for approximately 10% to 15% of all breast cancers.1,2 This subtype is more common in patients who are premenopausal, Black, and have BRCA1 gene mutations.2,3 Invasive ductal carcinoma is the most common phenotype of triple-negative breast cancer, accounting for 14.6% of patients with triple-negative disease.2

Treatment decisions in this case were based on NCCN and MD Anderson Cancer Center guidelines.4,5 The first step was to determine whether the patient had invasive versus noninvasive cancer. In this case, because the patient had cancer cells present in lymph nodes and invasive disease on left breast biopsy, the invasive protocol was followed. Based on the treatment guidelines for stage III, triple-negative disease, it was recommended that the patient consider neoadjuvant chemotherapy followed by total mastectomy with axillary lymph node surgery. This differs from the protocol for earlier stage, hormone-positive tumors, for which neoadjuvant chemotherapy is not considered. Because the patient had stage III disease with 4 or more involved lymph nodes, her treatment team also recommended postmastectomy radiation therapy focused on the chest wall and regional lymphatics. Because the patient was estrogen and progesterone receptor-negative, endocrine therapy to decrease these hormones in the body to reduce the risk for recurrence or spread of disease was not indicated. The patient also was not a candidate for targeted ERBB2 therapy because she was ERBB2-negative.

The patient received a cold cap during treatment, which is associated with a significant reduction in alopecia among patients receiving chemotherapy with a taxane, anthracycline, or both.6 Cold caps work by narrowing the blood vessels beneath the skin to reduce the effect of chemotherapy drugs near the hair follicles.

For surveillance, the patient should have a clinical breast exam every 3 to 6 months for 5 years, then annually after year 5.7 Because the patient had a total mastectomy on the left side, she does not need mammography of her left breast but should continue annual right breast screening mammography. The patient did not undergo immediate breast reconstruction because of the need for radiation after mastectomy. If she desires reconstruction in the future, she can be referred to a reconstructive surgeon to discuss options. Reconstructive surgery should not take place any sooner than 6 to 12 months after completion of radiation to allow the tissues time to heal.1

Conclusion

Triple-negative breast cancer is the most aggressive breast cancer phenotype. It is considered aggressive because the tumor grows and spreads quickly and is more likely to recur after treatment. Targeted therapy options for this type of malignancy are limited. The 5-year survival rate for patients with regional triple-negative breast cancer (has spread outside the breast to nearby structures or lymph nodes) is 65%, compared with approximately 90% survival rate for localized triple-negative disease and other breast cancer types.3,8 Patients must be monitored closely for side effects while receiving chemotherapy and radiation therapy and followed closely for recurrence and metastasis.

Sunayana Chopra Pydah, MBA, MHA, MPAM, PA-C, works in the department of pediatrics at Santa Clara Valley Medical Center in San Jose, California; Erin Hernandez, PA-C, works in the surgical oncology department at MD Anderson Cancer Center in Houston, Texas, and has over 13 years of experience in treating patients with breast cancer; and Melissa Shaffron, MPAS, PA-C, works in emergency and urgent care medicine. She serves as the associate program director and director of Clinical Education for the University of Lynchburg School of PA Medicine in Virginia.

References

1. National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Cancer stat facts: female breast cancer. Accessed August 22, 2021. https://seer.cancer.gov/statfacts/html/breast.html

2. Plasilova ML, Hayse B, Killelea BK, Horowitz NR, Chagpar AB, Lannin DR. Features of triple-negative breast cancer: analysis of 38,813 cases from the national cancer database. Medicine (Baltimore). 2016;95(35):e4614. doi:10.1097/MD.0000000000004614

3. Howard FM, Olopade OI. Epidemiology of triple-negative breast cancer: a review. Cancer J. 2021;27(1):8-16. doi:10.1097/PPO.0000000000000500

4. National Comprehensive Cancer Network. Breast cancer (version 6.2021). August 16, 2021. Accessed August 22, 2021. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf

5. MD Anderson Cancer Center. Breast cancer—invasive stage I-III. Accessed August 22, 2021. https://www.mdanderson.org/content/dam/mdanderson/documents/for-physicians/algorithms/cancer-treatment/ca-treatment-breast-invasive-web-algorithm.pdf

6. Nangia J, Wang T, Osborne C, et al. Effect of a scalp cooling device on alopecia in women undergoing chemotherapy for breast cancer: the SCALP randomized clinical trial. JAMA. 2017;317(6):596-605. doi:10.1001/jama.2016.20939

7. Smith TJ. Breast cancer surveillance guidelines. J Oncol Pract. 2013; 9(1): 65-67. doi:10.1200/JOP.2012.000787

8. American Cancer Society. Triple-negative breast cancer. Accessed August 22, 2021. https://www.cancer.org/cancer/breast-cancer/about/types-of-breast-cancer/triple-negative.html