Microinvasive breast carcinoma

INTRODUCTION — Microinvasive breast carcinoma is defined as invasive carcinoma of the breast with no invasive focus measuring more than 1 mm [1]. It is most commonly encountered in the setting of ductal carcinoma in situ (DCIS); thus, it is usually referred to as DCIS with microinvasion. It is less frequently seen in association with lobular carcinoma in situ (LCIS) or in the absence of carcinoma in situ.

The epidemiology, clinical presentation, pathology, and treatment of microinvasive breast carcinoma will be reviewed here. DCIS and LCIS are presented separately.

●(See "Ductal carcinoma in situ: Treatment and prognosis".)

●(See "Breast ductal carcinoma in situ: Epidemiology, clinical manifestations, and diagnosis".)

●(See "Atypia and lobular carcinoma in situ: High-risk lesions of the breast".)

●(See "Pathology of breast cancer".)

OVERVIEW — Data about the epidemiology and clinical significance of microinvasive breast carcinoma have been limited by its uncommon incidence and the historical lack of a standardized definition.

Epidemiology — The incidence of microinvasive breast carcinoma appears to have increased in parallel with the rising incidence of ductal carcinoma in situ (DCIS), which has been attributed primarily to the introduction of breast cancer screening programs as well as more thorough sampling of breast tissue specimens.

Nevertheless, pure microinvasive breast carcinoma (without associated DCIS) remains an uncommon disease, estimated as accounting for less than 1 percent of all breast cancers [2,3]. As with invasive breast cancer, microinvasive breast carcinoma is predominantly ductal in histologic type.

Risk factors for microinvasive breast carcinoma appear to be similar to those associated with DCIS, such as nulliparity and family history of breast cancer [2,3]. It occurs over a wide age range (30 to 85 years of age), with the average age in the 50 to 60s [3,4]. Case series have also suggested that patients diagnosed with microinvasive breast carcinoma have a high incidence of other high-risk lesions, including concurrent breast carcinoma and other malignancies, present at the time of diagnosis [2,3].

The epidemiology of DCIS is presented separately. (See "Breast ductal carcinoma in situ: Epidemiology, clinical manifestations, and diagnosis".)

Definition, pathology, and staging — Microinvasive breast carcinoma is defined by the American Joint Committee on Cancer and the International Union for Cancer Control (AJCC-UICC) as invasive carcinoma of the breast with no focus measuring more than 1 mm [5]. It is most commonly encountered in the setting of DCIS, where small foci of tumor cells have invaded through the basement membrane into the surrounding stroma. It is rarely seen in association with lobular carcinoma in situ (LCIS) or in the absence of carcinoma in situ [4]. Where associated with LCIS, the microinvasive component is usually lobular or occasionally tubular in histologic type.

According to the eighth edition Tumor, Node, Metastasis staging system as well as the preceding seventh edition, microinvasive breast carcinoma is designated as T1mi, as presented in the respective tables (table 1 and table 2). In cases with multiple foci of microinvasion (where no focus is larger than 1 mm), the number of foci and range of sizes should be reported. Note that the sizes of individual foci of microinvasion are not added together. Since microinvasive breast carcinoma may present with multiple foci of invasion, the pathologic specimen should be carefully examined for additional foci [6,7].

Histopathologically, microinvasive breast carcinoma tends to be associated with high-grade DCIS and comedo-type necrosis [2,8-10]. There is also evidence that the risk of microinvasion increases with larger-size DCIS lesions and multicentric DCIS [8-10]. (See "Pathology of breast cancer".)

There is little information about biologic markers such as estrogen receptor (ER) and progesterone receptor (PR) status and human epidermal growth factor receptor 2 (HER2) overexpression in microinvasive breast carcinoma [2,11,12]. In a study including 30 patients who had complete hormone receptor testing of both the invasive and in situ components, ER/PR positivity was 100 percent concordant in both microinvasive and in situ disease; ER negativity was 83 percent concordant. HER2 status was 100 percent concordant [13]. Contrary to invasive breast cancer, the limited data suggest that receptor expression has little prognostic significance in microinvasive breast cancer. (See 'Prognosis' below.)

Clinical presentation — Microinvasive breast carcinoma commonly presents within a palpable mass that represents an area of DCIS with stromal desmoplasia [2-4,8,9,14-16]. The microinvasion in and of itself is not palpable. Nipple discharge rarely may also occur.

Others have found that, similar to DCIS, the most frequent imaging appearance is calcifications [2]. These different results are likely due to differences between studies in the definition of microinvasive breast carcinoma used, which imaging studies were performed (ie, mammography or ultrasonography), and degree of tissue sampling. For example, a retrospective review of 37 patients with microinvasive breast cancer and 44 patients with intraductal carcinoma found that the most dominant magnetic resonance imaging (MRI) finding of both lesions was heterogeneous enhancement of non-mass-like lesions [17].

Most diagnostic biopsies are performed as core needle biopsies. As such, pathology results may only reveal DCIS or DCIS with a focus "suspicious for" microinvasion. It is only when the entire lesion is removed that a complete evaluation can be performed and a final diagnosis of invasive or microinvasive breast carcinoma can be rendered.

TREATMENT

Management of the breast — There are no randomized trials to inform the optimal surgical treatment for microinvasive breast carcinoma. Breast-conserving surgery (BCS) followed by radiation therapy (RT) for most patients with microinvasive breast carcinoma is appropriate. However, mastectomy (without RT) may be preferred for patients in whom the ductal carcinoma in situ (DCIS) component is large, high grade, with or without comedo necrosis and in whom clean margins cannot be definitively obtained with BCS.

BCS may be associated with an increased risk of local recurrence; RT after BCS minimizes this risk. For those with pure microinvasive carcinoma, margin requirements are the same as for those with invasive carcinoma (ie, no tumor on ink); however, for microinvasive carcinoma associated with DCIS, the larger margin requirements needed for DCIS are required. (See "Adjuvant radiation therapy for women with newly diagnosed, non-metastatic breast cancer" and "Ductal carcinoma in situ: Treatment and prognosis" and "Breast-conserving therapy" and "Mastectomy".)

As with DCIS and early invasive breast cancer, BCS for microinvasive breast carcinoma appears to achieve excellent outcomes [13,18]. In a retrospective study of 321 patients with DCIS and 72 patients with microinvasion treated with BCS, the presence of microinvasion did not correlate with local recurrence rate, distant relapse-free survival, or overall survival at almost nine years of follow-up [18]. The improved outcomes in contemporary series may be due at least in part to the use of adjuvant endocrine therapy for patients whose disease is estrogen receptor positive.

The risk of recurrence following BCS for microinvasive disease appears to be increased with:

●Positive excision margins [13,19] (see 'Prognosis' below)

●Size of the DCIS component [3,4]

●Unfavorable histopathologic characteristics of the associated DCIS component (ie, presence of comedo necrosis and high nuclear grade) [9]

As described above, these characteristics are common with microinvasive breast carcinoma. (See 'Overview' above.)

Management of the axilla — The reported incidence of axillary lymph node involvement in microinvasive breast carcinoma ranges from 0 to 20 percent but is generally 5 percent or less for properly defined microinvasive breast carcinoma [4,8,19-28]. The likelihood of axillary node involvement is greater in cases where stromal invasion is demonstrated by clusters of cells rather than single cells [6,8,14,15].

Although the majority of patients with microinvasive breast carcinoma are likely to have negative axillary lymph nodes, we proceed with a sentinel lymph node biopsy for patients in whom the assessment of axillary lymph node status will influence adjuvant therapy decisions. Omission of the sentinel lymph node for select older women with hormone-positive disease is discussed elsewhere. (See "Overview of the approach to early breast cancer in older women", section on 'Management of the axilla'.)

The importance of identifying nodal metastasis in T1mi patients should be further investigated to determine the impact, if any, on local-regional recurrence or distant disease [27,28]. (See "Overview of sentinel lymph node biopsy in breast cancer" and "Overview of sentinel lymph node biopsy in breast cancer", section on 'DCIS with suspicious features'.)

PROGNOSIS — Microinvasive breast carcinoma has an excellent prognosis, with a five-year overall survival between 97 and 100 percent [9]. Survival seems to be intermediate between pure ductal carcinoma in situ (DCIS) and small invasive carcinomas [11].

For women with microinvasive carcinoma, the risk of recurrence following surgery (breast-conserving therapy or mastectomy) appears to be small. In one study of 83 patients followed for a median of six years, the cumulative incidence of recurrence at five years was 5 percent [13]. The postexcision finding of close or positive margins (≤2 mm) on pathologic evaluation was the only factor associated with an increased risk of a local recurrence, which was diagnosed in 4 of 20 patients who had a close margin versus 2 of 62 who had a negative margin (hazard ratio 8.8, 95% CI 1.6-48.8). This small study also reported that overexpression of human epidermal growth factor 2 was not associated with the risk of axillary node involvement at diagnosis or the risk of recurrence.

IS THERE A ROLE FOR ADJUVANT SYSTEMIC THERAPY? — There have been no clinical trials specifically addressing the role of adjuvant endocrine therapy, chemotherapy, and/or trastuzumab in the treatment of microinvasive breast carcinoma. In the absence of definitive data, we treat microinvasive cancer similarly to ductal carcinoma in situ (DCIS), specifically:

●Adjuvant endocrine therapy is appropriate for most women with hormone receptor (HR)-positive microinvasive breast cancer. In this instance, the role of endocrine therapy is as "chemoprevention" either for the remaining breast tissue or the contralateral side, since the odds of distant recurrence and mortality from the microinvasive carcinoma are so low. The approach to these patients is similar to that for women with DCIS. (See "Ductal carcinoma in situ: Treatment and prognosis", section on 'Endocrine therapy'.)

●Given that by definition these patients have a primary breast tumor ≤1 mm, chemotherapy is not administered in the absence of nodal involvement. For patients who have microinvasive disease in the breast who are found concurrently to have metastatic disease in the lymph nodes, decisions regarding chemotherapy depend on receptor status and risk factors of the cancer. (See "Deciding when to use adjuvant chemotherapy for hormone receptor-positive, HER2-negative breast cancer" and "ER/PR negative, HER2-negative (triple-negative) breast cancer", section on 'Non-metastatic disease' and "Adjuvant systemic therapy for HER2-positive breast cancer".)

●The prognostic significance of hormone and/or human epidermal growth factor 2 (HER2) receptor expression is uncertain due to the paucity of available data. Often, there is not enough tissue for hormone and HER2 analysis. (See 'Prognosis' above.)

The evidence underlying these recommendations for adjuvant therapy for early-stage breast cancer is discussed separately. (See "Overview of the treatment of newly diagnosed, invasive, non-metastatic breast cancer".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Ductal carcinoma in situ".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Ductal carcinoma in situ (DCIS) (The Basics)")

SUMMARY AND RECOMMENDATIONS — Microinvasive breast carcinoma is defined as invasive carcinoma of the breast with no focus measuring more than 1 mm; it is invariably encountered in the setting of ductal carcinoma in situ (DCIS).

●Overview – The risk of microinvasive breast carcinoma increases with larger-size DCIS lesions and multicentric DCIS. It tends to be associated with high-grade DCIS and DCIS with comedo necrosis and in that setting is more likely to present with multiple foci of microinvasion. (See 'Overview' above.)

According to the eighth edition American Joint Committee on Cancer and the International Union for Cancer Control Tumor, Node, Metastasis staging system, microinvasive breast carcinoma is designated as T1mi. (See 'Overview' above.)

●Management of the breast – The optimal treatment for microinvasive breast cancer is undefined. We suggest breast-conserving surgery (BCS) followed by radiation therapy to reduce the risk of local recurrence (Grade 2B). However, mastectomy may be preferred for patients at high risk of local recurrence with breast-conserving therapy, including those with extensive, multicentric, high-grade DCIS, with or without comedo necrosis and for those patients when histologically clear margins cannot be obtained with BCS. (See 'Management of the breast' above.)

●Management of the axilla – We proceed with sentinel lymph node biopsy (SLNB) for patients with confirmed microinvasive breast carcinoma in whom the assessment of axillary lymph node status will influence adjuvant therapy decisions (see 'Management of the axilla' above). Omission of SLNB for older women with hormone receptor-positive breast cancer is discussed elsewhere. (See "Overview of the approach to early breast cancer in older women", section on 'Management of the axilla'.)

●Prognosis – Microinvasive breast carcinoma has an excellent prognosis, with a greater than 95 percent five-year overall survival. (See 'Prognosis' above.)

●Adjuvant systemic therapy – Adjuvant endocrine therapy is appropriate for most women with hormone receptor (HR)-positive microinvasive breast cancer. In this instance, the role of endocrine therapy is as "chemoprevention" either for the remaining breast tissue or the contralateral side, since the odds of distant recurrence and mortality from microinvasive carcinoma are so low. The approach to these patients is similar to that for women in invasive HR-positive breast cancer. (See "Adjuvant endocrine and targeted therapy for postmenopausal women with hormone receptor-positive breast cancer".)

Given that by definition these patients have a primary breast tumor ≤1 mm, chemotherapy is not administered in the absence of nodal involvement. For patients who have microinvasive disease in the breast who are found concurrently to have macrometastatic disease to the lymph nodes, decisions regarding chemotherapy depend on receptor status and risk factors of the cancer. (See "Selection and administration of adjuvant chemotherapy for HER2-negative breast cancer" and "Adjuvant systemic therapy for HER2-positive breast cancer".)